Search Results (254)

Amorpha fruticosa L. (Fabaceae) originates from North America and has become an aggressive invasive plant in many parts of the world. It affects the local biodiversity in many negative ways. Our previous in vivo tests of purified extract of A. fruticosa pods for antihyperglycemic activity in streptozotocin-induced diabetic spontaneously hypertensive rats (SHRs) revealed that the oral administration of purified extract of A. fruticosa (100 mg/kg) for 35 days to SHRs caused significant decreases in the systolic pressure, blood glucose levels, and MDA quantity. The aim of this experimental study is to test the glycosidase inhibition of several extracts of A. fruticosa pods. Methods: GC-MS, NMR, and a glycosidase inhibition assay were performed. Results: The results demonstrate strong inhibition of yeast alpha- and almond beta-glucosidases, rat intestinal hexosaminidase, and bovine beta-glucuronidase, but not of some other glycosidases. The activity is probably due at least in part to the presence of iminosugars and iminosugar acids. We here report on further analysis and activity assessments of A. fruticosa pods and leaves collected in Bulgaria, and for the first time discover glycosidase inhibitors, pinitol, and hydroxylated pipecolic acids in the species and more complex iminosugar-like compounds that may all contribute to antidiabetic potential. Hydroxylated pipecolic acids are probable precursors of iminosugars and common in legumes containing them. Considerable chemical variation was observed over four pod collections. Conclusions: A. fruticosa pods and leaves were found to contain a number of compounds that could contribute to the potential antihyperglycemic activities including pinitol and a complex mixture of iminosugar-related compounds derived from pipecolic acids and prolines. The pods and leaves caused potent selective inhibition of glucosidases and hexosaminidases and beta-glucuronidase. The variation between the collections might reflect the sites differing or wide phenotypic versatility allowing the success of the species as an invasive plant. Full article

Nicotine-induced oxidative stress contributes significantly to vascular endothelial dysfunction. While negative air ions (NAIs) demonstrate potential blood-pressure-regulating and antioxidant properties, their mechanistic role remains unclear. This study examined the effects of NAIs against nicotine-induced oxidative damage and vascular endothelial injury in spontaneously hypertensive rats (SHRs). Western blotting was used to detect the expression levels of the α7nAChR/MAPK/AP1 pathway. Transcriptomic sequencing was performed to identify the differentially expressed genes after treatment with nicotine or NAIs. Furthermore, reactive oxygen species (ROS), endothelin-1 (ET-1), and [Ca²⁺]_i levels were detected in human aortic endothelial cells (HAECs) treated with nicotine, and the relationship between transcription factor activator protein 1 (AP1) and the target genes was further elucidated through ChIP–qPCR. Nicotine exposure in SHRs elevated blood pressure and induced oxidative damage through α7nAChR/MAPK/AP1 pathway activation, causing endothelial structural disruption. These effects manifested as decreased NO/eNOS and increased ET-1/ET_ab expression, while these changes were reversed by NAIs. In HAECs, nicotine impaired proliferation while increasing oxidative stress and [Ca²⁺]_i levels. This endothelial damage was markedly attenuated by either NAIs or fibronectin 1 (Fn1)/secreted phosphoprotein 1 (Spp1) knockdown. Mechanistically, we identified AP1 as the transcriptional regulator of FN1 and SPP1. NAIs attenuate nicotine-induced endothelial dysfunction in hypertension by inhibiting AP1-mediated FN1 and SPP1 activation, providing novel insights for smoking-associated cardiovascular risk. Full article

Background/Objectives: Hypertension is a major contributor to cardiovascular diseases and is often intensified by psychological stress, which can also affect bone metabolism. Although both conditions independently compromise bone health, their combined impact—particularly under acute and chronic stress—remains unclear. This pilot study aimed to assess the effects of such stressors on bone structure in spontaneously hypertensive rats (SHRs). Methods: Forty male rats, both normotensive and SHRs, were randomly assigned to control, acute stress, or chronic stress groups. Acute stress involves a single 2 h physical restraint. Chronic stress was induced over 10 days using alternating stressors: agitation, forced swimming, physical restraint, cold exposure, and water deprivation. Tibial bones were analyzed by microcomputed tomography (micro-CT), and histology was performed using Hematoxylin and Eosin and Masson’s Trichrome stains. Results: Micro-CT showed increased trabecular bone volume in normotensive rats under chronic stress, whereas SHRs displayed impaired remodeling under both stress types. Histological analysis revealed preserved connective tissue overall but evident changes in growth plate structure among stressed rats. SHRs exhibited exacerbated trabecular formation and cartilage abnormalities, including necrotic zones. Conclusions: Both acute and chronic stress, especially in the context of hypertension, negatively affect bone remodeling and maturation. Despite the absence of overt inflammation, structural bone changes were evident, indicating potential long-term risks. These findings highlight the importance of further studies on stress–hypertension interactions in bone health as well as the exploration of therapeutic approaches to mitigate skeletal damage under such conditions. Full article

Background/Objectives: Metabolic syndrome is one of the leading causes of mortality worldwide, with high-fat diet (HFD) intake being a significant driving force. Despite long-term research, new interventions are still being sought to improve cardiovascular disorders associated with metabolic syndrome. Methods: To explore the therapeutic potential of a slow-releasing H₂S donor, we evaluated the effects of 3 weeks of treatment with GYY-4137 on systolic blood pressure (sBP), cardiac parameters, adiposity, selected plasma markers, and the vascular function of the thoracic aortas (TAs) and mesenteric arteries (MAs) isolated from male spontaneously hypertensive rats (SHRs) fed an HFD for 8 weeks. Results: HFD administration induced cardiac remodeling, increased adiposity, and decreased adrenergic contractility in both TAs and MAs. Moreover, although high-fat intake improved TAs relaxation, it decreased aortic protein expression of endothelial NO synthase and the involvement of NO in vasoactive responses of both TAs and MAs. In addition, protein expression of inducible NOS and tumor necrosis factor alpha (TNFα) in aortas was increased, as were plasma levels of chemerin, which has been proposed as a possible link among metabolic and vascular disorders and inflammation. Treatment with GYY-4137 reduced sBP, improved relaxation of the MAs, partially restored the contractility of the TAs, generally restored NO signaling, and decreased the protein expression of the inducible NOS and TNFα, as well as plasma chemerin levels. Conclusions: A slow H₂S-releasing donor could partially ameliorate the metabolic changes induced by increased fat intake during essential hypertension and trigger beneficial vasoactive effects associated with the NO signaling restoration and suppression of inflammation. Full article

Background: Systemic arterial hypertension is one of the leading global health concerns, significantly increasing the risk of cardiovascular and kidney diseases, including nephrolithiasis. The treatment, still far from ideal, is constantly undergoing new alternatives. In this context, medicinal plants rich in flavonoids, such as naringenin—a compound found in citrus fruits—have gained attention for their potential diuretic, nephroprotective, and blood pressure-lowering effects. Objectives: This study aimed to evaluate the effects of naringenin (100 mg/kg, orally) over nine days on blood pressure, renal function, and calcium oxalate crystal formation in normotensive Wistar (NTR) and spontaneously hypertensive male rats (SHR). Methods: Key assessments included blood pressure and heart rate measurements in vivo, urine volume and electrolyte excretion in vivo, in vitro calcium oxalate crystallization, and in silico molecular docking analyses to investigate molecular interactions. Results: Naringenin treatment significantly reduced blood pressure and increased diuresis in both NTR and SHR groups, while a notable natriuretic effect was observed specifically in NTR. In vitro, naringenin reduced the formation of calcium oxalate crystals in urines from NTR. Molecular docking studies suggested that these effects may be mediated by interactions with SGLT1 and SGLT2 transporters, potentially explaining the diuretic and natriuretic outcomes. Additionally, interactions with MMP-9 and β2-adrenergic receptors may contribute to the reduction in crystal formation. Conclusions: Collectively, these findings indicate that repeated administration of naringenin exerts beneficial effects on both cardiovascular and renal parameters, and point to promising molecular targets that may underlie its protective actions. Full article

Background/Objectives: Variations of the latrophilin-3 (Lphn3) gene have been associated with attention-deficit hyperactivity disorder (ADHD). To explore the functional influence of this gene, Lphn3 knockout (KO) rats were generated and have thus far demonstrated deficits in ADHD-relevant phenotypes, including working memory, impulsivity, and hyperactivity. However, inattention remains unexplored. Methods: We assessed automatic attention in Lphn3 KO (n = 19) and their control line (wildtype/WT, n = 20) through use of the following auditory event-related potentials (ERPs): P1, N1, P2, and N2. We also extended this exploratory study by comparing these same ERPs in spontaneously hypertensive rats (SHRs, n = 16), the most commonly studied animal model of ADHD, to their control line (Wistar–Kyoto/WKY, n = 20). Electroencephalograms (EEG) were recorded using subdermal needle electrodes at frontocentral sites while freely moving rats were presented with five-tone trains (50 ms tones, 400 ms tone onset asynchronies) with varying short (1 s) and long (5 s) inter-train intervals. Peak amplitudes and latencies were analyzed using GLM-mixed ANOVAs to assess differences across genotypes (KO vs. WTs) and strains (SHRs vs. WKYs). Results: The KOs did not demonstrate any significant differences in peak amplitudes relative to the WT controls, suggesting that the null expression of Lphn3 does not result in the development of inefficiencies in automatic attention. However, the SHRs exhibited significantly reduced peak P1 (and peak-to-peak P1–N1) values relative to the WKYs. These attenuations likely reflect inefficiencies in bottom-up arousal networks that are necessary for efficient automatic processing. Conclusions: Distinct findings between these animal models likely reflect differing alterations in dopamine and noradrenaline neurotransmission that may underlie ADHD-relevant phenotypes. Full article

Background/Objectives: The kidney plays a crucial role in regulating normal blood pressure and is one of the major organs affected by hypertension. The present study aimed to investigate the hypotensive and renoprotective effects of four specific green tea peptides extracted from green tea dregs on spontaneously hypertensive rats (SHRs) and to investigate the underlying mechanisms. Methods: Four specific green tea peptides (40 mg/kg) were gavaged to SHRs for 4 weeks, and blood pressure, renal function, renal pathological changes, renal tissue fibrosis indexes, and inflammation indexes were examined in SHRs to analyze the role of the four green tea peptides in alleviating hypertension and its renal injury. Results: The results showed that the four TPs significantly reduced systolic and diastolic blood pressure (20–24% and 18–28%) in SHR compared to the model group. Meanwhile, gene levels and protein expression of renal fibrosis-related targets such as phospho-Smad2/3 (p-Smad2/3) (26–47%), Sma- and Mad-related proteins 2/3 (Smad2/3) (19–38%), transforming growth factor-β1 (TGF-β1) (36–63%), and alpha-smooth muscle actin (alpha-SMA) (58–86%) were also significantly reduced. In addition, the reduced expression levels of medullary differentiation factor 88 (MyD88) (14–36%), inducible nitric oxide synthase (iNOS) (58–73%), and nuclear factor-κB p65 (NF-kB p65) (35–78%) in kidneys also confirmed that TPs attenuated renal inflammation in SHR. Therefore, green tea peptides could attenuate the fibrosis and inflammatory responses occurring in hypertensive kidneys by inhibiting the Ang II/TGF-β1/SMAD signaling pathway and MyD88/NF-κB p65/iNOS signaling pathway. Conclusions: The results showed that green tea peptides may be effective candidates for lowering blood pressure and attenuating kidney injury. Full article

Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder that significantly impacts learning, daily functioning, and personal development. Astaxanthin (ASTA), a naturally occurring antioxidant, has garnered interest as a potential therapeutic agent for various diseases, particularly in mitigating oxidative stress. This study explores a novel application of ASTA in the context of ADHD, aiming to investigate its therapeutic effects and underlying mechanisms. Spontaneously hypertensive rats (SHRs), widely used ADHD model animals, were treated with ASTA (50/100 mg/kg/day) for three weeks, 5 mg/kg/day atomoxetine (ATO) as the positive, and Wistar Kyoto (WKY) rats as control. Behavioral improvements were assessed using the open field test (OFT) and the Morris water maze (MWM). Biochemical analyses were conducted to evaluate changes in the levels of various neurotrophic factors, while histological examinations were performed to assess neuroprotective effects. Additionally, the role of ASTA in the brain–gut axis was investigated. The behavioral symptoms of hyperactivity, anxiety, and impaired spatial memory in ADHD animals were mitigated by ASTA. This improvement is primarily attributed to the restoration of neurotransmitter levels, particularly dopamine (DA), achieved through the modulation of several critical components within the dopamine system, including dopamine receptor 1 (DR1), dopamine transporter (DAT), tyrosine hydroxylase (TH), and synaptic-associated protein 25 (SNAP-25). Additionally, regulating the serotonin transporter (SERT) and glial cell-derived neurotrophic factor (GDNF) supports the recovery of serotonin levels and facilitates optimal brain development. Furthermore, cerebellar cells were protected, and the structure of the intestinal microbiota was regulated. ASTA can mitigate ADHD symptoms in SHR through the modulation of the dopaminergic system, multiple neurotransmitters, neurotrophic factors, and the neuro-intestinal environment, which establishes ASTA as a promising nutraceutical candidate for adjunctive therapy in pediatric ADHD. Full article

Empagliflozin (EMPA), a sodium-glucose co-transporter 2 (SGLT2) inhibitor, prevents endothelial dysfunction, but its effects on vascular tone in hypertension remain unclear. This study investigated whether EMPA modulates vasomotor tone via sirtuin 1 (SIRT1) and AMP-activated protein kinase (AMPK) pathways in spontaneously hypertensive rats (SHR) and controls (Wistar Kyoto rats, WKY). Functional (wire myography, organ bath) and biochemical (Western blot) studies were conducted on the third-order of the superior mesenteric arteries (sMAs) and/or aortas. EMPA induced concentration-dependent relaxation of preconstricted sMAs in both groups. In SHR, EMPA enhanced acetylcholine (Ach)-induced relaxation in sMAs and aortas and reduced constriction induced by phenylephrine (Phe) and U46619 in sMAs. The SIRT1 inhibitor (EX527) abolished EMPA’s effects on Ach-mediated relaxation and U46619-induced vasoconstriction, while AMPK inhibition reduced Ach-mediated relaxation and Phe-induced vasoconstriction. SHR showed increased SGLT2 and SIRT1 expression and decreased pAMPK/AMPK levels in sMAs. In conclusion, EMPA might exert vasoprotective effects in hypertension by enhancing endothelium-dependent relaxation and reducing constriction via AMPK/SIRT1 pathways. These properties could improve vascular health in patients with hypertension and related conditions. Further studies are needed to explore new indications for SGLT2 inhibitors. Full article

Using an atrial fibrillation (AF) model in spontaneously hypertensive rats (SHRs), we aimed to identify circulating miRNAs for AF diagnosis and prediction and to confirm the cardiac origin of these miRNAs. A total of 31 SHRs and 39 Wistar Kyoto (WKY) normotensive controls were randomized into six groups: young, adult, and aging SHR and WKY. Spontaneous AF burden and atrial and circulating levels of 11 miRNAs were quantified. Spontaneous AF was absent in all WKY rats. In the SHRs, AF episodes were observed in two adult animals and in all aging animals (13.6 ± 2.3 episodes/24 h). The atrial levels of five miRNAs were significantly higher in adult and aging SHRs compared to their WKY controls (all p < 0.05). Of these, only the circulating levels of miR-328 were significantly higher in the aging SHRs vs. WKYs (p < 0.0001). Atrial miR-328 levels in the SHRs increased progressively with age (p < 0.001) and correlated with circulating miR-328 levels (r = 0.58; p < 0.01). Among aging SHRs, atrial levels of miR-328 strongly correlated with AF burden (r = 0.79; p < 0.01). These data suggest that the circulating level of miR-328 could emerge as a promising marker for both AF diagnosis and, if assessed dynamically, for AF prediction. Full article

The carotid body (CB), the main peripheral arterial chemoreceptor, exhibits considerable structural and neurochemical plasticity in response to pathological conditions such as high blood pressure. Previous studies have shown that morphological alterations in the hypertensive CB are characterized by enlarged parenchyma due to cellular hypertrophy and hyperplasia, and vasodilation. To test whether hypertension can also induce neoangiogenesis and modulate its chemosensory function, we examined the immunohistochemical expression of two angiogenic factors, vascular endothelial growth factor (VEGF) and endothelin-1 (ET), and their corresponding receptors in the CB of adult spontaneously hypertensive rats (SHRs), and compared their expression patterns to that of age-matched normotensive Wistar rats (NWR). We found an increased VEGF-A and B, and VEGFR-2 expression in glomus and endothelial cells in the enlarged CB glomeruli of SHRs compared with that in NWR. Conversely, weaker immunoreactivity to VEGFR-1 was detected in cell clusters of the hypertensive CB. The expression of endothelin-converting enzyme 1 and its receptor ETA was higher in a subset of glomus cells in the normotensive CB, while the immunoreactivity to the ETB receptor was enhanced in endothelial cells of CB blood vessels in SHRs. The elevated endothelial expression of VEGF and ET-1 suggests their role as local vascular remodeling factors in the adaptation to hypertension, though their involvement in the cellular rearrangement and modulation of chemosensory function could also be implied. Full article

Traumatic brain injury (TBI) is one of the primary causes of mortality and disability, with arterial blood pressure being an important factor in the clinical management of TBI. Spontaneously hypertensive rats (SHRs), widely used as a model of essential hypertension and vascular dementia, demonstrate dysfunction of the hypothalamic–pituitary–adrenal axis, which may contribute to glucocorticoid-mediated hippocampal damage. The aim of this study was to assess acute post-TBI seizures, delayed mortality, and hippocampal pathology in SHRs and normotensive Sprague Dawley rats (SDRs). Male adult SDRs and SHRs were subjected to lateral fluid-percussion injury. Immediate seizures were video recorded, corticosterone (CS) was measured in blood plasma throughout the study, and hippocampal morphology assessed 3 months post-TBI. Acute and remote survival rates were significantly higher in the SHRs compared to the SDRs (overall mortality 0% and 58%, respectively). Immediate seizure duration predicted acute but not remote mortality. TBI did not affect blood CS in the SHRs, while the CS level was transiently elevated in the SDRs, predicting remote mortality. Neuronal cell loss in the polymorph layer of ipsilateral dentate gyrus was found in both the SDRs and SHRs, while thinning of hippocampal pyramidal and granular cell layers were strain- and area-specific. No remote effects of TBI on the density of astrocytes or microglia were revealed. SHRs possess a unique resilience to TBI as compared with normotensive SDRs. SHRs show shorter immediate seizures and reduced CS response to the injury, suggesting the development of long-term adaptative mechanisms associated with chronic hypertension. Though remote post-traumatic hippocampal damage in ipsilateral dentate gyrus is obvious in both SHRs and SDRs, the data imply that physiological adaptations to high blood pressure in SHRs may be protective, preventing TBI-induced mortality but not hippocampal neurodegeneration. Understanding the mechanisms of resilience to TBI may also help improve clinical recommendations for patients with hypertension. Limitation: since more than a half of the SDRs with prolonged immediate seizures or elevated CS 3 days after TBI have died, survivorship bias might hamper correct interpretation of the data. Full article

Hypertension is a global health concern not only correlated with cardiovascular complications, but also with impaired bone metabolism, potentially affecting healing at the bone–implant interface. Losartan, an angiotensin II receptor blocker (ARB) commonly prescribed for hypertension, has shown beneficial effects on bone healing in spontaneously hypertensive rats (SHRs). However, the influence of hypertension and ARBs like losartan on the bone cellular response at the bone–implant interface remains underexplored. Methods: A total of 32 rats were included in this study: 16 SHRs, with 8 receiving losartan (30 mg/kg daily) and 8 receiving no treatment, and 16 normotensive Wistar rats, with 8 receiving losartan and 8 receiving no treatment. After one week of treatment, titanium implants were placed into the tibia of all the animals. The bone–implant interface was assessed 60 days post-implantation using micro-computed tomography (µCT) and an immunohistochemical analysis. Results: (i) The ARB treatment significantly increased the bone volume and bone–implant contact in the SHRs receiving losartan compared to the untreated SHRs. (ii) Consistent with the µCT findings, the immunohistochemistry further confirmed regular bone turnover and increased osteocalcin (OC) mineralization in the treated SHRs. In contrast, no alterations in the bone microarchitecture were noted in the Wistar rats treated with losartan. Conclusions: The results suggest that losartan, an ARB drug, improves bone volume and bone turnover at the bone–implant interface in SHRs. Full article

This study investigates the effects of alcoholic (AB) and non-alcoholic beer (NAB) consumption on blood pressure and the activity of enzymes regulating the renin–angiotensin system (RAS) in Wistar–Kyoto (WKY) and spontaneously hypertensive rats (SHRs), with WKY rats used as normotensive controls for SHRs. The RAS is crucial for long-term blood pressure regulation, with angiotensin II (AngII) being a potent vasoconstrictor. The aim was to explore the biochemical mechanisms by which beer might influence cardiovascular health. WKY and SHRs were divided into groups receiving tap water (TW), non-alcoholic beer (NAB), alcoholic beer (AB), TW or NAB and TW or AB for 12 weeks. Systolic blood pressure (SBP), body weight, and biochemical parameters (electrolytes, glucose, renal and liver function, lipid profile) were monitored, and the RAS enzyme activity in serum and various tissues was analyzed. Beer consumption, regardless of alcohol content, did not significantly affect SBP or body weight. However, NAB and AB altered the serum electrolyte levels in both strains. AB consumption increased liver enzyme activity. Significant changes were observed in the RAS enzyme activity across tissues, varying by strain, beer type, and tissue. Moderate beer consumption did not elevate blood pressure in WKY or SHRs. Nevertheless, beer modulated RAS-regulating enzyme activities, indicating potential impacts on cardiovascular homeostasis. Full article

Attention deficit/hyperactivity disorder (ADHD) is defined as a neurodevelopmental condition. The precise underlying mechanisms remain incompletely elucidated. A body of research suggests disruptions in both the cellular architecture and neuronal function within the brain regions of individuals with ADHD, coupled with disturbances in the biochemical parameters. This study seeks to evaluate the morphological characteristics with a volume measurement of the striatal regions and a neuron density assessment within the studied areas across different developmental stages in Spontaneously Hypertensive Rats (SHRs) and Wistar Kyoto Rats (WKYs). Furthermore, the investigation aims to scrutinize the levels and activities of specific markers related to immune function, oxidative stress, and metabolism within the striatum of juvenile and maturing SHRs compared to WKYs. The findings reveal that the most pronounced reductions in striatal volume occur during the juvenile stage in SHRs, alongside alterations in neuronal density within these brain regions compared to WKYs. Additionally, SHRs exhibit heightened levels and activities of various markers, including RAC-alpha serine/threonine-protein kinase (AKT-1), glucocorticoid receptor (GCsRβ), malondialdehyde (MDA), sulfhydryl groups (-SH), glucose (G), iron (Fe), lactate dehydrogenase (LDH). alanine transaminase (ALT), and aspartate transaminase (AST). In summary, notable changes in striatal morphology and elevated levels of inflammatory, oxidative, and metabolic markers within the striatum may be linked to the disrupted brain development and maturation observed in ADHD. Full article