Nitric Oxide and its Effects on Vasculature and Blood Pressure: A Narrative Review

Introduction

The regulation of blood pressure and maintenance of vascular health are critical components of cardiovascular function, with nitric oxide (NO) playing a pivotal role. NO is a key signaling molecule involved in endothelial function and hemodynamics. (Abolfazli et al. 2024, Smith et al. 2020) Early research, particularly the pioneering work of Dr. Marc C. Houston in the 1990s, highlighted the necessity of understanding NO’s role, along with cofactors, lifestyle changes, and nutritional adaptations, in preventing inflammation and NO deficiencies.(Houston et al. 1998, Houston et al. 1999, Dmytriv et al. 2024) Since then, numerous studies have advanced this field, especially in recent years.(Gonzalez et al. 2023) This research consists of a narrative review of the scientific and medical literature to present the latest findings on NO’s effects on endothelial function and blood pressure regulation. By sourcing from PubMed, using keywords such as “Nitric Oxide,” “endothelial dysfunction,” “blood pressure,” “vascular integrity,” and “hypertension,” this review seeks to enhance the current understanding of NO’s role in maintaining vascular integrity and managing hypertension.

This research aims to present and analyze the latest studies and information on the effects of NO on endothelial function and hemodynamics, with a particular focus on blood pressure regulation. Building upon the foundational work of Dr. Marc C. Houston from the 1990s (Houston et al. 1998, Houston et al. 1999, Dmytriv et al. 2024), this research aims to integrate updated findings from studies conducted post-2018. The goal is to enhance the current understanding of how NO, cofactors, lifestyle changes, and nutritional adaptations significantly prevent damage caused by inflammation and NO deficiencies. This review will explore the impact of NO specifically on vascular integrity and, thus, on hypertension. In doing so, this review will address a singular factor in the multifactorial nature of hypertension while also exploring the role of NO in other health issues.

Database Utilization: PubMed was the primary source for gathering relevant research studies and meta-analyses. Keyword Application: Specific keywords, including “Nitric Oxide,” “endothelial dysfunction,” “blood pressure,” “vascular integrity,” and “hypertension,” were employed to identify pertinent studies. Data Filtering: The search results were filtered to include studies conducted post-2018, thus ensuring the inclusion of the most recent and relevant findings.

NO plays a crucial role in maintaining endothelial function and regulating blood pressure and, consequently, is vital to vascular health. (Meza et al. 2019, Shaito et al. 2022, Smith et al. 2020, Wautier et al. 2022) NO enhances vascular integrity and prevents inflammation-related damage. (Dri et al. 2023) The vascular endothelium functions as a fairly active endocrine organ, regulating the vascular tone to maintain vascular homeostasis. The endothelial cells also control glucose catabolism by way of insulin. By affecting hexokinase, the first enzyme of glycolysis, which phosphorylates glucose to glucose-6-phosphate, insulin enables the glucose to move from the blood into skeletal muscle cells. (Meza et al. 2019) Meanwhile, in healthy individuals, insulin also stimulates blood flow by way of endothelium-dependent vasodilation, but this mechanism is disrupted in settings of type 2 diabetes and cardiovascular disease. (Battillo et al. 2024) The vascular endothelium of such patients exhibits poor REDOX control, resulting in a shift toward overproduction by NADPH oxidases (NOX) of reactive oxygen species. (Battillo et al. 2024) Consequently, hyperglycemia, and thus diabetes mellitus, have been hypothesized to induce an imbalance between NOX and endothelial NO synthase (eNOS). Therefore, NO may be key to the pathophysiology connecting type 2 diabetes to its vascular complications (Meza at al. 2019). Meanwhile, due to its action on vascular smooth muscle, NO is also a potent regulator of blood pressure, meaning that NO-related therapies could potentially be employed by physicians and other clinicians for managing patients’ blood pressure according to guidelines of professional organizations, such as the American Heart Association and the American College of Cardiology. (Iqbal and Jamal 2023, Shaito et al. 2022, Virani et al. 2023)

Chronic vascular encephalopathy (CVE), a frequent cause of cognitive impairment, constitutes another vascular disease in whose pathophysiology disrupted NO pathways may play a key role. Not only is the study of CVE in connection with NO informing the development of NO-related therapeutics for this condition, but it also improves the understanding of post-hypoxic reperfusion injury of the brain. (Dmytriv et al. 2024) A range of studies suggest that pharmacological interventions, lifestyle changes, and nutritional factors together can play a role in optimizing cardiovascular health, partly via NO-related effects.(Gonzalez et al. 2023) Interventions may be applicable not only as interventions against disease but also for enhancing performance. Regarding NO and performance, supplements containing agents known to release or cause the release of NO have become popular among bodybuilders and other athletes, based on the hypothesis that NO’s stimulation of blood flow in muscle tissue will aid muscle growth. Such agents in supplements on the market include L-arginine, L-citrulline, citrulline malate, and various nitrates. However, the efficacy of such products remains to be validated, and the purity and dosages of such agents in supplements vary significantly due to the fairly loose regulation of supplements compared with pharmaceuticals. (Gonzalez et al. 2023)

Conclusion

Understanding the effects of NO on endothelial function and hemodynamics is vital for developing effective strategies to manage blood pressure and improve overall cardiovascular health There is a knowledge gap, so there is a need for ongoing investigation into NO at all levels: basic science-level translational research level clinical trial level Future exploration should address existing gaps and should build on the current body of knowledge to advance therapeutic approaches.

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