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Special Issue "Antihypertensive Drugs"

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A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (30 November 2009)

Special Issue Editors

Guest Editor
Prof. Dr. Giuseppe Mancia

Clinical Medicine Unit, University of Milano-Bicocca, San Gerardo Hospital, Via Pergolesi, 33, 20052 Monza (MI), Italy
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Fax: +39 039 322274
Interests: pathophysiology; clinical pharmacology and therapy of hypertension; congestive heart failure and other cardiovascular diseases
Guest Editor
Prof. Dr. Guido Grassi

Dipartimento di Medicina Clinica, Università Milano-Bicocca, Ospedale San Gerardo di Monza, Italy
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Special Issue Information

Dear Colleagues,

Hypertension has not always been recognized as a harbinger of cardiovascular complications and premature death. Only 70 years ago, hypertension was considered the body's adaptation to sclerotic blood vessel disease and essential to maintain organ perfusion; thus, treatment was regarded as undesirable. Epidemiologic studies have since established a strong linear relation between blood pressure and cardiovascular disease (CVD), and randomized trials have documented that blood pressure reductions by antihypertensive drugs confer cardiovascular protection, making the hypertension-related risk a reversible risk. There is now a consensus that blood pressure should be reduced to <140/90 mm Hg in all patients and that a more aggressive blood pressure target (<130/80 mm Hg) should be pursued in those in whom the cardiovascular risk is high. Despite this, blood pressure control remains elusive in most individuals in the hypertensive population, which makes improvement of blood pressure control in this population a priority goal. This goal may meet with new challenges, however. Optimal blood pressure control may have to include the measurement of blood pressure every day, given the fluctuations of blood pressure and their prognostic importance independent of and in addition to that of classically measured blood pressure values. This special issue of the journal will provide an up-to-date and comprehensive review of the drugs currently used in antihypertensive treatment.

Prof. Dr. Giuseppe Mancia
Prof. Dr. Guido Grassi
Guest Editors

Keywords

  • hypertension
  • antihypertensive treatment
  • ace-inhibitors
  • angiotensin II receptor blockers
  • diuretics
  • calcium antagonists
  • beta-blockers
  • blood pressure control
  • cardiovascular risk
  • clinical trials

Published Papers (17 papers)

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Research

Jump to: Review, Other

Open AccessArticle Degradation of Methyldopa by Banana
Pharmaceuticals 2010, 3(3), 441-447; doi:10.3390/ph3030441
Received: 18 December 2009 / Revised: 12 February 2010 / Accepted: 2 March 2010 / Published: 2 March 2010
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Abstract
Methyldopa, an antihypertensive, is a very close analogue of DOPA. Drug interaction accompanied by degradation in a banana juice mixture was reported for DOPA. However, the effect of banana on methyldopa has not been reported. Therefore, we have investigated the impact of banana
[...] Read more.
Methyldopa, an antihypertensive, is a very close analogue of DOPA. Drug interaction accompanied by degradation in a banana juice mixture was reported for DOPA. However, the effect of banana on methyldopa has not been reported. Therefore, we have investigated the impact of banana juice on methyldopa. The drug and supernatant of banana pulp were mixed, and the mixture was observed for changes in color, drug concentration, and ultraviolet-visible absorption spectra at 30 °C. The originally clear and colorless mixture started to acquire a yellow coloration after about 30 seconds after the mixing. The color tone increasingly deepened, then blistered solid particles that do not dissolve were observed after 3 hours. Concentration of methyldopa in the mixture decreased by 60% after 5 min, to 0.5% after 30 min of the mixing. From these findings, it was suggested that the drastic alterations were caused by banana polyphenol oxidase that plays a role in the biosynthesis of melanin pigment from levodopa in banana pulp. Because the degradation of methyldopa occurs extremely fast, it was suggested concomitant use of this anti-hypertensive and banana juice consumption should be avoided in clinical practice. Full article
(This article belongs to the Special Issue Antihypertensive Drugs)
Open AccessArticle A New Baroreceptor Sensitivity-Restoring Ca-Channel Blocker Diminishes Age-Related Morning Blood Pressure Increase in Hypertensive Patients: Open-Label Monitoring of Azelnidipine Treatment for Hypertension in the Early Morning (At-HOME) Study
Pharmaceuticals 2010, 3(1), 225-236; doi:10.3390/ph3010225
Received: 1 December 2009 / Revised: 28 December 2009 / Accepted: 5 January 2010 / Published: 19 January 2010
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Abstract
Background: Morning blood pressure (BP) surge, which exhibits an age-related increase, is a risk factor for stroke in elderly hypertensive patients, independently of the 24-h BP level. We studied the effect of the new baroreceptor sensitivity (BRS)-restoring Ca-channel blocker (CCB) azelnidipine (AZ) on
[...] Read more.
Background: Morning blood pressure (BP) surge, which exhibits an age-related increase, is a risk factor for stroke in elderly hypertensive patients, independently of the 24-h BP level. We studied the effect of the new baroreceptor sensitivity (BRS)-restoring Ca-channel blocker (CCB) azelnidipine (AZ) on this age-related morning BP increase. Methods: We conducted a 16-week prospective study to clarify the effect of morning dosing of AZ on home BPs measured in the morning and in the evening in 2,546 hypertensive patients (mean age, 65.1 years; female, 53.6%). Results: At baseline, ME-Dif (morning systolic BP [SBP]–evening SBP) increased with age, independently of ME-Ave (average of the morning and evening SBPs). This age-related increase of ME-Dif was exaggerated by regular alcohol drinking and beta-blocker use. After AZ treatment (14.3 ± 3.6 mg/day), ME-AV and ME-Dif were significantly reduced independently of each other, with reductions of –18.1 ± 15.6 and –2.5 ± 13.2 mmHg, respectively (both p < 0.001). AZ treatment decreased age-related increase in ME-Dif particularly in patients who were regular consumers of alcohol and in beta-blocker users. Conclusions: The new BRS-restoring CCB AZ significantly reduced age-related increase in morning BP and had some potential benefit on cardiovascular protection in hypertension, particularly in elderly patients and/or consumers of alcohol. Full article
(This article belongs to the Special Issue Antihypertensive Drugs)
Open AccessArticle Spironolactone Plus Full-Dose ACE Inhibition in Patients with Idiopathic Membranous Nephropathy and Nephrotic Syndrome: Does It Really Work?
Pharmaceuticals 2010, 3(1), 1-9; doi:10.3390/ph3010001
Received: 2 December 2009 / Revised: 29 December 2009 / Accepted: 31 December 2009 / Published: 5 January 2010
Cited by 5 | PDF Full-text (86 KB) | HTML Full-text | XML Full-text
Abstract
We have studied the effects of add-on spironolactone treatment (100 mg/day) in 11 patients with idiopathic membranous nephropathy (IMN) and > 3 gm proteinuria/day despite angiotensin converting enzyme (ACE) inhibitor therapy titrated to a systolic/diastolic blood pressure
[...] Read more.
We have studied the effects of add-on spironolactone treatment (100 mg/day) in 11 patients with idiopathic membranous nephropathy (IMN) and > 3 gm proteinuria/day despite angiotensin converting enzyme (ACE) inhibitor therapy titrated to a systolic/diastolic blood pressure < 120/80 mmHg. Blood pressure, 24-hour urinary protein excretion, and creatinine clearance were measured prior to, after two months of combined therapy, and after a 2-month withdrawal period of spironolactone. While systolic and diastolic blood pressure decreased significantly after spironolactone therapy, proteinuria did not improve. Serum potassium increased significantly as well, with three patients requiring resin-binding therapy. Thus, spironolactone seems to have no additional antiproteinuric effects over ACE inhibitor therapy in patients with IMN and nephrotic syndrome and carries the risk of significant hyperkalemia. Full article
(This article belongs to the Special Issue Antihypertensive Drugs)
Open AccessArticle The Soluble Epoxide Hydrolase Inhibitor AR9281 Decreases Blood Pressure, Ameliorates Renal Injury and Improves Vascular Function in Hypertension
Pharmaceuticals 2009, 2(3), 217-227; doi:10.3390/ph2030217
Received: 10 November 2009 / Revised: 12 December 2009 / Accepted: 16 December 2009 / Published: 18 December 2009
Cited by 7 | PDF Full-text (901 KB) | HTML Full-text | XML Full-text
Abstract
Soluble epoxide hydrolase inhibitors (sEHIs) are demonstrating promise as potential pharmaceutical agents for the treatment of cardiovascular disease, diabetes, inflammation, and kidney disease. The present study determined the ability of a first-inclass sEHI, AR9281, to decrease blood pressure, improve vascular function, and decrease
[...] Read more.
Soluble epoxide hydrolase inhibitors (sEHIs) are demonstrating promise as potential pharmaceutical agents for the treatment of cardiovascular disease, diabetes, inflammation, and kidney disease. The present study determined the ability of a first-inclass sEHI, AR9281, to decrease blood pressure, improve vascular function, and decrease renal inflammation and injury in angiotensin hypertension. Rats were infused with angiotensin and AR9281 was given orally during the 14-day infusion period. Systolic blood pressure averaged 180 ± 5 mmHg in vehicle treated and AR9281 treatment significantly lowered blood pressure to 142 ± 7 mmHg in angiotensin hypertension. Histological analysis demonstrated decreased injury to the juxtamedullary glomeruli. Renal expression of inflammatory genes was increased in angiotensin hypertension and two weeks of AR9281 treatment decreased this index of renal inflammation. Vascular function in angiotensin hypertension was also improved by AR9281 treatment. Decreased afferent arteriolar and mesenteric resistance endothelial dependent dilator responses were ameliorated by AR9281 treatment of angiotensin hypertensive rats. These data demonstrate that the first-in-class sEHI, AR9281, lowers blood pressure, improves vascular function and reduces renal damage in angiotensin hypertension. Full article
(This article belongs to the Special Issue Antihypertensive Drugs)
Open AccessArticle Combination Therapy with Olmesartan and Amlodipine in the Treatment of Hypertension
Pharmaceuticals 2009, 2(3), 125-133; doi:10.3390/ph2030125
Received: 26 November 2009 / Accepted: 30 November 2009 / Published: 1 December 2009
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Abstract
Background: Combination therapy with antihypertensive agents utilises different mechanisms of action and may be responsible for a more effective decrease in blood pressure. Objective: To review the recently published trials on efficacy and safety of the combination therapy with olmesartan and amlodipine. Results:
[...] Read more.
Background: Combination therapy with antihypertensive agents utilises different mechanisms of action and may be responsible for a more effective decrease in blood pressure. Objective: To review the recently published trials on efficacy and safety of the combination therapy with olmesartan and amlodipine. Results: The double-blind American COACH (Combination of Olmesartan Medoxomil and Amlopdine Besylate in Controlling High Blood Pressure) study (2008) showed in 1,940 patients that after eight weeks of treatment the BP goals were most frequently achieved in the ‘combination therapy group’, with 56.3% (54.1–58.5%) and 54.0% (51.8–56.2%) of patients reaching adequate blood pressure of <140/90 mmHg with olmesartan/amlodipine 20/10 and 40/10 respectively. Combination therapy was generally well tolerated. The most common side effect was oedema [olmesartan 20 mg 9.9% (8.6–11.3%), amlodipine 10 mg 36.8% (34.7–39.0%), placebo 12.3% (10.9–13.8%)]. The frequency of oedema was lower in the groups combining amlodipine 10 mg with olmesartan 10 mg (26.5%, 24.5–28.5%), 20 mg (25.6%, 23.7–27.6%) or 40 mg (23.5%, 21.6–25.4%). In 2009 three double-blind controlled European studies including 500–1,000 patients each and performed independently of one another have confirmed the above study, and have demonstrated similar efficacy-safety effects from the combination of olmesartan medoxomil with amlodipine, particularly for patients not achieving adequate blood pressure control with olmesartan monotherapy. Conclusions: Combinations of olmesartan and amlodipine were significantly more effective at reducing blood pressure and realising guideline blood pressure goals in patients with mild to severe hypertension than monotherapy (with a placebo component). Combination therapy is well tolerated and is associated with a lower incidence of side effects, such as oedema, compared to monotherapy with high amlodipine dosages (10 mg). Full article
(This article belongs to the Special Issue Antihypertensive Drugs)
Open AccessArticle Obsessive-Compulsive and Post Traumatic Avoidance Symptoms Influence the Response to Antihypertensive Therapy: Relevance in Uncontrolled Hypertension
Pharmaceuticals 2009, 2(3), 82-93; doi:10.3390/ph2030082
Received: 22 September 2009 / Revised: 9 November 2009 / Accepted: 13 November 2009 / Published: 16 November 2009
Cited by 1 | PDF Full-text (169 KB) | HTML Full-text | XML Full-text
Abstract
Aim: To investigate the association of uncontrolled hypertension with psychological factors associated with high cardiovascular morbidity and mortality (type D personality, depression, posttraumatic stress-related symptoms). Methods: 205 consecutive outpatient hypertensives completed three questionnaires evaluating Type D personality (DS 16), post traumatic
[...] Read more.
Aim: To investigate the association of uncontrolled hypertension with psychological factors associated with high cardiovascular morbidity and mortality (type D personality, depression, posttraumatic stress-related symptoms). Methods: 205 consecutive outpatient hypertensives completed three questionnaires evaluating Type D personality (DS 16), post traumatic symptoms (revised Impact of Events Scale), symptoms of anxiety, hostility, depression and obsessive-compulsive traits (subscales of the Symptom Checklist). Uncontrolled hypertension was diagnosed when clinic sitting blood pressure was above 140/90 mmHg (130/80 in the presence of diabetes or nephropathy), despite reported adherence to treatment with at least three antihypertensive medications, including a diuretic. Results: Uncontrolled hypertension (39%), was predicted by lower scores at Symptom Checklist obsessive-compulsive subscale and higher number of post traumatic avoidance symptoms, older age, diabetes, higher systolic pressure at first visit and longstanding hypertension. Type D personality correlated with depression, hostility, anxiety, compulsiveness, history of malignancy, and older age, but not with uncontrolled hypertension. Conclusions: Uncontrolled hypertension is associated with low obsessionality and avoidance symptoms, which reduce compliance to treatment. On the contrary, type D personality is not correlated with uncontrolled hypertension, as it includes compulsiveness, which improves compliance. A multidisciplinary approach to the hypertensive patient is mandatory to establish if the psychological profile affects compliance. Full article
(This article belongs to the Special Issue Antihypertensive Drugs)

Review

Jump to: Research, Other

Open AccessReview Blood Pressure-Lowering Aspects of Lipid-Lowering and Anti-Diabetic Drugs
Pharmaceuticals 2011, 4(1), 1-6; doi:10.3390/ph4010001
Received: 20 December 2010 / Accepted: 22 December 2010 / Published: 23 December 2010
Cited by 1 | PDF Full-text (36 KB) | HTML Full-text | XML Full-text
Abstract
Several studies have shown that blood pressure can be lowered by the use of drugs that are not traditional antihypertensive drugs. This might be of clinical importance when many risk patients are treated by combination drug therapy in order to prevent cardiovascular disease
[...] Read more.
Several studies have shown that blood pressure can be lowered by the use of drugs that are not traditional antihypertensive drugs. This might be of clinical importance when many risk patients are treated by combination drug therapy in order to prevent cardiovascular disease by way of improving the cardiovascular risk factor profile. Full article
(This article belongs to the Special Issue Antihypertensive Drugs)
Open AccessReview The Renin-Angiotensin System in the Development of Salt-Sensitive Hypertension in Animal Models and Humans
Pharmaceuticals 2010, 3(4), 940-960; doi:10.3390/ph3040940
Received: 22 December 2009 / Revised: 25 February 2010 / Accepted: 8 March 2010 / Published: 29 March 2010
Cited by 5 | PDF Full-text (98 KB) | HTML Full-text | XML Full-text
Abstract
Hypertension is still one of the major causes of death from cardiovascular failure. Increased salt intake may aggravate the rise in blood pressure and the development of consequential damage of the heart, the vessels and other organs. The general necessity of restricted salt
[...] Read more.
Hypertension is still one of the major causes of death from cardiovascular failure. Increased salt intake may aggravate the rise in blood pressure and the development of consequential damage of the heart, the vessels and other organs. The general necessity of restricted salt intake regardless of blood pressure or salt sensitivity has been a matter of debate over the past decades. This review summarizes the main pathogenic mechanisms of hypertension and salt sensitivity in rat models, particularly in the spontaneously hypertensive rat (SHR), and in patients with essential hypertension (EH). Although SHRs are commonly considered to be salt-resistant, there is much evidence that salt loading may deteriorate blood pressure and cardiovascular function even in these animals. Similarly, EH is not a homogenous disorder – some patients, but not all, exhibit pronounced salt sensitivity. The renin-angiotensin system (RAS) plays a key role in the regulation of blood pressure and salt and fluid homeostasis and thus is one of the main targets of antihypertensive therapy. This review focuses on the contribution of the RAS to the pathogenesis of salt-sensitive hypertension in SHRs and patients with EH. Full article
(This article belongs to the Special Issue Antihypertensive Drugs)
Figures

Open AccessReview Combating Combination of Hypertension and Diabetes in Different Rat Models
Pharmaceuticals 2010, 3(4), 916-939; doi:10.3390/ph3040916
Received: 5 January 2010 / Revised: 4 March 2010 / Accepted: 18 March 2010 / Published: 26 March 2010
Cited by 1 | PDF Full-text (206 KB) | HTML Full-text | XML Full-text
Abstract
Rat experimental models are used extensively for studying physiological mechanisms and treatments of hypertension and diabetes co-existence. Each one of these conditions is a major risk factor for cardiovascular disease (CVD), and the combination of the two conditions is a potent enhancer of
[...] Read more.
Rat experimental models are used extensively for studying physiological mechanisms and treatments of hypertension and diabetes co-existence. Each one of these conditions is a major risk factor for cardiovascular disease (CVD), and the combination of the two conditions is a potent enhancer of CVD. Five major animal models that advanced our understanding of the mechanisms and therapeutic approaches in humans are discussed in this review: Zucker, Goto-Kakizaki, SHROB, SHR/NDmcr-cp and Cohen Rosenthal diabetic hypertensive (CRDH) rats. The use of various drugs, such as angiotensin-converting enzyme (ACE) inhibitors (ACEIs), various angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs), to combat the effects of concomitant pathologies on the combination of diabetes and hypertension, as well as the non-pharmacological approach are reviewed in detail for each rat model. Results from experiments on these models indicate that classical factors contributing to the pathology of hypertension and diabetes combination—Including hypertension, hyperglycemia, hyperinsulinemia and hyperlipidemia—can now be treated, although these treatments do not completely prevent renal complications. Animal studies have focused on several mechanisms involved in hypertension/diabetes that remain to be translated into clinical medicine, including hypoxia, oxidative stress, and advanced glycation. Several target molecules have been identified that need to be incorporated into a treatment modality. The challenge continues to be the identification and interpretation of the clinical evidence from the animal models and their application to human treatment. Full article
(This article belongs to the Special Issue Antihypertensive Drugs)
Open AccessReview Home and Office Blood Pressure Control among Treated Hypertensive Patients in Japan: Findings from the Japan Home versus Office Blood Pressure Measurement Evaluation (J-HOME) Study
Pharmaceuticals 2010, 3(2), 419-432; doi:10.3390/ph3020419
Received: 14 December 2009 / Revised: 29 January 2010 / Accepted: 2 February 2010 / Published: 4 February 2010
PDF Full-text (148 KB) | HTML Full-text | XML Full-text
Abstract
Appropriate control of blood pressure (BP) is essential for prevention of future cardiovascular events. However, BP control among treated hypertensive patients has been insufficient. Recently, the usefulness of self-measured BP at home (home BP measurement) for the management of hypertension has been reported
[...] Read more.
Appropriate control of blood pressure (BP) is essential for prevention of future cardiovascular events. However, BP control among treated hypertensive patients has been insufficient. Recently, the usefulness of self-measured BP at home (home BP measurement) for the management of hypertension has been reported in many studies. We evaluated BP control both at home and in the office among treated hypertensive patients in primary care settings in Japan (the J-HOME study). We found poor control of home and office BPs and clarified some factors affecting control. We also examined factors associated with the magnitude of the white-coat effect, the morning–evening BP difference, and home heart rate in this J-HOME study. Full article
(This article belongs to the Special Issue Antihypertensive Drugs)
Open AccessReview Quercetin: A Treatment for Hypertension?—A Review of Efficacy and Mechanisms
Pharmaceuticals 2010, 3(1), 237-250; doi:10.3390/ph3010237
Received: 8 December 2009 / Revised: 12 January 2010 / Accepted: 14 January 2010 / Published: 19 January 2010
Cited by 26 | PDF Full-text (108 KB) | HTML Full-text | XML Full-text
Abstract
Quercetin is a polyphenolic flavonoid. Common sources in the diet are apples, onions, berries, and red wine. Epidemiological studies have found an inverse relationship between dietary quercetin intake and cardiovascular disease. This has led to in vitro, in vivo, and clinical
[...] Read more.
Quercetin is a polyphenolic flavonoid. Common sources in the diet are apples, onions, berries, and red wine. Epidemiological studies have found an inverse relationship between dietary quercetin intake and cardiovascular disease. This has led to in vitro, in vivo, and clinical research to determine the mechanism by which quercetin exerts cardioprotective effects. Recent studies have found a reduction in blood pressure when hypertensive (>140 mm Hg systolic and >90 mm Hg diastolic) animals and humans are supplemented with quercetin. Proposed mechanisms for the antihypertensive effect of quercetin include decreased oxidative stress, inhibition of angiotensin converting enzyme activity, improved endothelial function, direct action on the vascular smooth muscle, and/or modulation in cell signaling and gene expression. Although in vitro and in vivo evidence exists to support and refute each possibility, it is likely that quercetin influences multiple targets via a combination of known and as yet undiscovered mechanisms. The purpose of this review is to examine the mechanisms whereby quercetin might reduce blood pressure in hypertensive individuals. Full article
(This article belongs to the Special Issue Antihypertensive Drugs)
Open AccessReview Antihypertensive Peptides from Milk Proteins
Pharmaceuticals 2010, 3(1), 251-272; doi:10.3390/ph3010251
Received: 23 December 2009 / Revised: 14 January 2010 / Accepted: 18 January 2010 / Published: 19 January 2010
Cited by 53 | PDF Full-text (211 KB) | HTML Full-text | XML Full-text
Abstract
Dietary proteins possess a wide range of nutritional and functional properties. They are used as a source of energy and amino acids, which are needed for growth and development. Many dietary proteins, especially milk proteins, contain physiologically active peptides encrypted in the protein
[...] Read more.
Dietary proteins possess a wide range of nutritional and functional properties. They are used as a source of energy and amino acids, which are needed for growth and development. Many dietary proteins, especially milk proteins, contain physiologically active peptides encrypted in the protein sequence. These peptides may be released during gastrointestinal digestion or food processing and once liberated, cause different physiological functions. Milk-derived bioactive peptides are shown to have antihypertensive, antimicrobial, immunomodulatory, antioxidative and mineral-binding properties. During the fermentation of milk with certain lactobacilli, two interesting tripeptides Ile-Pro-Pro and Val-Pro-Pro are released from casein to the final product. These lactotripeptides have attenuated the development of hypertension in several animal models and lowered blood pressure in clinical studies. They inhibit ACE in vitro at micromolar concentrations, protect endothelial function in vitro and reduce arterial stiffness in humans. Thus, milk as a traditional food product can after certain processing serve as a functional food and carry specific health-promoting effects, providing an option to control blood pressure. Full article
(This article belongs to the Special Issue Antihypertensive Drugs)
Open AccessReview A Novel Category of Anti-Hypertensive Drugs for Treating Salt-Sensitive Hypertension on the Basis of a New Development Concept
Pharmaceuticals 2010, 3(1), 59-109; doi:10.3390/ph3010059
Received: 24 October 2009 / Revised: 24 December 2009 / Accepted: 6 January 2010 / Published: 7 January 2010
Cited by 3 | PDF Full-text (1857 KB) | HTML Full-text | XML Full-text
Abstract
Terrestrial animals must conserve water and NaCl to survive dry environments. The kidney reabsorbs 95% of the sodium filtered from the glomeruli before sodium reaches the distal connecting tubules. Excess sodium intake requires the renal kallikrein-kinin system for additional excretion. Renal kallikrein is
[...] Read more.
Terrestrial animals must conserve water and NaCl to survive dry environments. The kidney reabsorbs 95% of the sodium filtered from the glomeruli before sodium reaches the distal connecting tubules. Excess sodium intake requires the renal kallikrein-kinin system for additional excretion. Renal kallikrein is secreted from the distal connecting tubule cells of the kidney, and its substrates, low molecular kininogen, from the principal cells of the cortical collecting ducts (CD). Formed kinins inhibit reabsorption of NaCl through bradykinin (BK)-B2 receptors, localized along the CD. Degradation pathway of BK by kinin-destroying enzymes in urine differs completely from that in plasma, so that ACE inhibitors are ineffective. Urinary BK is destroyed mainly by a carboxypeptidase-Y-like exopeptidase (CPY) and partly by a neutral endopeptidase (NEP). Inhibitors of CPY and NEP, ebelactone B and poststatin, respectively, were found. Renal kallikrein secretion is accelerated by potassium and ATP-sensitive potassium (KATP) channel blockers, such as PNU-37883A. Ebelactone B prevents DOCA-salt hypertension in rats. Only high salt intake causes hypertension in animals deficient in BK-B2 receptors, tissue kallikrein, or kininogen. Hypertensive patients, and spontaneously hypertensive rats, excrete less kallikrein than normal subjects, irrespective of races, and become salt-sensitive. Ebelactone B, poststatin, and KATP channel blockers could become novel antihypertensive drugs by increase in urinary kinin levels. Roles of kinin in cardiovascular diseases were discussed. Full article
(This article belongs to the Special Issue Antihypertensive Drugs)
Open AccessReview Oxytocin: Old Hormone, New Drug
Pharmaceuticals 2009, 2(3), 168-183; doi:10.3390/ph203168
Received: 11 November 2009 / Revised: 1 December 2009 / Accepted: 2 December 2009 / Published: 9 December 2009
Cited by 7 | PDF Full-text (612 KB) | HTML Full-text | XML Full-text
Abstract
Oxytocin (OT), traditionally associated with reproductive functions, was revisited recently, and several new functions in cardiovascular regulation were discovered. These functions include stimulation of the cardioprotective mediators nitric oxide (NO) and atrial natriuretic peptide. OT’s cardiovascular outcomes comprise: (i) natriuresis, (ii) blood pressure
[...] Read more.
Oxytocin (OT), traditionally associated with reproductive functions, was revisited recently, and several new functions in cardiovascular regulation were discovered. These functions include stimulation of the cardioprotective mediators nitric oxide (NO) and atrial natriuretic peptide. OT’s cardiovascular outcomes comprise: (i) natriuresis, (ii) blood pressure reduction, (iii) negative inotropic and chronotropic effects, (iv) parasympathetic neuromodulation, (v) NO pathway involvement in vasodilatation and endothelial cell growth, (vi) anti-inflammatory and (vii) antioxidant activities as well as (viii) metabolic effects. In addition, we have reported abundant OT in the early developing heart with its capacity to generate cardiomyocytes (CMs) from mouse embryonic stem cells and stem cells residing in the heart. OT increases glucose uptake by cultured CMs, in normal, hypoxic and even in insulin resistance conditions. In experimentally-induced myocardial infarction in rats, continuous in vivo OT delivery improves the cardiac healing process and cardiac work, diminishes inflammation, and stimulates angiogenesis. Therefore, in pathological situations, OT plays an anti-inflammatory and cardioprotective role, enhancing vascular and metabolic functions, with potential therapeutic application(s). Full article
(This article belongs to the Special Issue Antihypertensive Drugs)
Open AccessReview Aliskiren: Just a New Drug for Few Selected Patients or an Innovative Molecule Predestinated to Replace Arbs and Ace-Inhibitors?
Pharmaceuticals 2009, 2(3), 118-124; doi:10.3390/ph2030118
Received: 21 October 2009 / Revised: 14 November 2009 / Accepted: 17 November 2009 / Published: 27 November 2009
Cited by 1 | PDF Full-text (41 KB) | HTML Full-text | XML Full-text | Correction | Supplementary Files
Abstract
The renin-angiotensin-aldosterone system (RAAS) plays a dominant role in the pathophysiology of hypertension, diabetes mellitus, chronic kidney disease and chronic heart failure. Therefore, drugs that block key components of the RAAS such as ACE inhibitors (ACEI) and angiotensin receptor blockers (ARBs) have gained
[...] Read more.
The renin-angiotensin-aldosterone system (RAAS) plays a dominant role in the pathophysiology of hypertension, diabetes mellitus, chronic kidney disease and chronic heart failure. Therefore, drugs that block key components of the RAAS such as ACE inhibitors (ACEI) and angiotensin receptor blockers (ARBs) have gained wide clinical use for these indications. Despite progress, the morbidity and mortality of patients treated with ACEI or ARBs remain high. Aliskiren (Tekturna, Rasilez) is the first orally active inhibitor of renin approved for clinical use as an antihypertensive agent. The development program has established that at the licensed doses of 150 mg and 300 mg. Aliskiren is effective either as monotherapy or in combination with drugs from the other major classes. In this review we analyze and review the information already gained with Aliskiren, raises questions regarding the advantages of DRIs as monotherapy compared to marketed ACEIs and ARBs, their potential added value in combination with other RAAS modulators and other still unproven benefits in relation to prorenin and renin receptor biology. Full article
(This article belongs to the Special Issue Antihypertensive Drugs)
Open AccessReview Hypertensive Emergency in Aortic Dissection and Thoracic Aortic Aneurysm—A Review of Management
Pharmaceuticals 2009, 2(3), 66-76; doi:10.3390/ph2030066
Received: 10 August 2009 / Revised: 21 September 2009 / Accepted: 27 September 2009 / Published: 28 September 2009
Cited by 6 | PDF Full-text (150 KB) | HTML Full-text | XML Full-text
Abstract
Over the last few decades, treatment for aortic dissection and thoracic aortic aneurysms has evolved significantly with improvement in outcomes. Treatment paradigms include medical, endovascular and surgical options. As aortic dissection presents as a hypertensive emergency, diligent control of BP is of utmost
[...] Read more.
Over the last few decades, treatment for aortic dissection and thoracic aortic aneurysms has evolved significantly with improvement in outcomes. Treatment paradigms include medical, endovascular and surgical options. As aortic dissection presents as a hypertensive emergency, diligent control of BP is of utmost importance in order to reduce the progression of dissection with possible aortic branch malperfusion. Treatment should begin on arrival to the emergency department and continues in the intensive care unit, endovascular suite or the operating room. Novel antihypertensive medications with improved pharmacological profile and improved surgical techniques, have improved the prognosis of patients with aortic aneurysm and/or aortic dissection. Nevertheless, morbidity and mortality remain high and hypertensive emergency poses a significant challenge in aortic dissection and thoracic aortic aneurysms. Full article
(This article belongs to the Special Issue Antihypertensive Drugs)

Other

Jump to: Research, Review

Open AccessOpinion Antihypertensive Drug and Inner Ear Perfusion: An Otologist’s Point of View
Pharmaceuticals 2009, 2(2), 44-48; doi:10.3390/ph2020044
Received: 23 July 2009 / Revised: 4 September 2009 / Accepted: 11 September 2009 / Published: 11 September 2009
Cited by 1 | PDF Full-text (30 KB) | HTML Full-text | XML Full-text
Abstract
A number of labyrinthine disorders with sensorineural hearing loss, vertigo, and tinnitus are known to occur to young people without vascular risk factors, thus being classified as “idiopathic” in the absence of satisfactory explanations; in the last decade, this phenomenon has found a
[...] Read more.
A number of labyrinthine disorders with sensorineural hearing loss, vertigo, and tinnitus are known to occur to young people without vascular risk factors, thus being classified as “idiopathic” in the absence of satisfactory explanations; in the last decade, this phenomenon has found a reliable explanation by the adverse effect of a sharp decrease of blood pressure values followed by an abnormal vasomotor regulation. This model may not only be applied to healthy subjects, but even had some confirmation in conditions possibly affecting hemodynamic changes, such as heart failure or treated hypertension. In particular, the results of a recent study on the impact of different antihypertensive therapies, which was analyzed by monitoring the onset or enhancement of tinnitus as a symptom of inner ear sufferance, unequivocally demonstrated an increased prevalence of tinnitus in subjects submitted to more “aggressive” treatments. This seems in agreement with recent observations about the model of fluid homeostasis of the inner ear, and suggests, when possible, to resort to treatments with modulatory effects in order to maintain a steady perfusion to the labyrinth thus protecting its function. Full article
(This article belongs to the Special Issue Antihypertensive Drugs)

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