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Molecular Mechanisms of Nitric Oxide in Cardiovascular System

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 August 2026 | Viewed by 2087

Special Issue Editor


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Guest Editor
Laboratory of Physiology, Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy
Interests: oxidative stress; cardiac function; mitochondrial function; aging; nitric oxide; physiology; NAFLD; microvesicles
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Special Issue Information

Dear Colleagues,

In the cardiovascular system, nitric oxide (NO), which is mainly produced by the endothelial NO synthase isoform, is highly involved in the modulation of vascular homeostasis and cardiac systo-diastolic function through mechanisms related to calcium handling and maintaining endothelial and mitochondrial function. Furthermore, due to its ability to interact with reactive oxygen species and activate the nitroso-redox signaling pathway, NO can play a central role in the pathophysiology of cardiovascular conditions. Hence, along with other factors, dysfunction in NO bioavailability or in downstream NO-related molecular mechanisms may result in the onset of hypertension, coronary disease, atherosclerosis, heart failure, and stroke. Despite the wide range of information available on this issue, however, unanswered questions about the signaling pathways and the control of NO bioactivity still remain. Increasing knowledge about this issue could be useful from the perspective of preventive medicine and therapeutic strategies. For the abovementioned reasons, this review aims to fill these gaps on the topic.

Dr. Elena Grossini
Guest Editor

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Keywords

  • heart
  • nitric oxide
  • oxidative stress
  • pathways
  • protection
  • therapy
  • vascular

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Published Papers (2 papers)

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Research

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14 pages, 1314 KB  
Article
Role of Oxidative Stress in the Neural Control of Intra-Renal Hemodynamics in Stroke-Prone Spontaneously Hypertensive Rats
by Ahmad Ahmeda, Zakarya Ahmeda, Yehia S. Mohamed and Mark G. Rae
Int. J. Mol. Sci. 2026, 27(2), 558; https://doi.org/10.3390/ijms27020558 - 6 Jan 2026
Viewed by 348
Abstract
Excessive oxidative stress within the renal medulla is implicated in the development of hypertension, potentially modulated by renal nerve stimulation (RNS). This study examined the effects of RNS on cortical and medullary blood perfusion in Stroke-Prone Spontaneously Hypertensive Rats (SHRSP) under both normal [...] Read more.
Excessive oxidative stress within the renal medulla is implicated in the development of hypertension, potentially modulated by renal nerve stimulation (RNS). This study examined the effects of RNS on cortical and medullary blood perfusion in Stroke-Prone Spontaneously Hypertensive Rats (SHRSP) under both normal conditions and at varying levels of oxidative stress. Male SHRSP rats were assigned to five experimental groups and subjected to RNS at different frequencies, with infusions of vehicle, tempol, tempol plus catalase (tem + cat), diethyldithiocarbamic acid (DETC), or L-nitro-arginine methyl ester (L-NAME) at the renal cortico-medullary border (CMB). Regional blood perfusion of the renal cortex and medulla (CBP and MBP, respectively) was assessed using Laser-Doppler flowmetry. RNS significantly reduced CBP and MBP by 43 ± 8% and 23 ± 4%, respectively, at 8 Hz. Co-infusion of tempol plus catalase significantly attenuated the RNS-induced reductions in both CBP and MBP. Similarly, DETC infusion mitigated RNS-induced decreases in CBP and MBP. In contrast, tempol alone and L-NAME did not protect against the RNS-induced under-perfusion of the renal cortex and medulla. The results suggest that simultaneous removal of superoxide anion and hydrogen peroxide (H2O2) can alleviate the reduction in renal blood perfusion caused by RNS, emphasizing a crucial role for H2O2 in renal hemodynamic regulation. Interestingly, DETC, which is expected to elevate superoxide anion levels, also mitigated RNS-induced under-perfusion, suggesting the presence of a potentially novel indirect protective mechanism that warrants further investigation. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Nitric Oxide in Cardiovascular System)
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Review

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29 pages, 1001 KB  
Review
Nitric Oxide Signaling in Cardiovascular Physiology and Pathology: Mechanisms, Dysregulation, and Therapeutic Frontiers
by Sakthipriyan Venkatesan, Carlo Smirne, Carmen Imma Aquino, Daniela Surico, Valentino Remorgida, Mohammad Mostafa Ola Pour, Mario Pirisi and Elena Grossini
Int. J. Mol. Sci. 2026, 27(2), 629; https://doi.org/10.3390/ijms27020629 - 8 Jan 2026
Viewed by 1445
Abstract
Nitric oxide (NO), a fundamental gaseous signaling molecule, is indispensable for cardiovascular homeostasis. This review synthesizes the expansive field of NO biology within the unifying framework of Nitric Oxide Equilibrium (NOE), i.e., the critical balance between its synthesis, bioavailability, and degradation. In a [...] Read more.
Nitric oxide (NO), a fundamental gaseous signaling molecule, is indispensable for cardiovascular homeostasis. This review synthesizes the expansive field of NO biology within the unifying framework of Nitric Oxide Equilibrium (NOE), i.e., the critical balance between its synthesis, bioavailability, and degradation. In a physiological state, NOE maintains vascular health by regulating blood pressure, preventing thrombosis, suppressing inflammation, and optimizing both cardiac and mitochondrial function. Here, we analyze how NOE disruption, primarily through oxidative stress and enzymatic dysfunction, underlies the pathogenesis of major cardiovascular diseases, including atherosclerosis, heart failure, ischemia–reperfusion injury, and cerebrovascular diseases like stroke. A critical evaluation of therapeutic strategies designed to restore NOE is presented, encompassing classic NO donors and phosphodiesterase-5 inhibitors, alongside next-generation soluble guanylate cyclase modulators and precision nanomedicine approaches. By identifying key knowledge gaps and methodological hurdles, this review charts a course for future research focused on biomarker-guided interventions and personalized medicine. Ultimately, we frame the restoration of NOE as a paramount therapeutic goal, crucial to translating decades of molecular research into effective clinical practice. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Nitric Oxide in Cardiovascular System)
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