Inhibiting Low-Density Lipoproteins Intimal Deposition and Preserving Nitric Oxide Function in the Vascular System
Christophe Wiart in Medicinal Plants in Asia for Metabolic Syndrome, 2017
Vascular endothelial cells release nitric oxide which relaxes and suppresses abnormal proliferation vascular smooth muscle cells and inhibit low-density lipoprotein oxidation involved in atherogenesis. Thus, inhibiting low-density lipoproteins intimal deposition and oxidation and preserving nitric oxide function in arteries constitutes one therapeutic strategy to prevent cardiovascular pathologies associated with diabetes and obesity. The progressive deposition of cholesteryl ester and fibrous elements in arterial intima leads to atherosclerosis. Hypertension is one of the greatest public health problems, and it is estimated that by 2025 about 60% of the world population will suffer from it. Atherogenesis encompasses the entry and chronic deposition of low-density lipoprotein in arterial intima. The antithrombotic and antiatherogenic properties of nitric oxide produced by endothelial cells are due to the ability of this signaling molecule to inhibit low-density lipoprotein oxidation, intimal vascular smooth muscle cells migration, and proliferation.
Nitric Oxide Is Said to Be the “Miracle Molecule” That “Reverses Aging”
Robert Fried, Lynn Nezin in Evidence-Based Proactive Nutrition to Slow Cellular Aging, 2017
This chapter focuses on a curious molecule, a gas actually, nitric oxide (NO), made by the cells in the inner lining of our blood vessels, the endothelium. The cells use an enzyme, nitric oxide synthase (NOS), to derive NO from the amino acid L-arginine, a component of protein in foods in the diet. Nitric oxide (NO) is formed from L-arginine by nitric oxide synthase enzymes (NOS), there being three isoforms: eNOS forms NO in the endothelium to control blood flow in the vessels; nNOS forms NO in nerve and brain cells to effect their communication; and inducible iNOS forms NO in macrophages activated to combat inflammation. Endothelial NO formation declines more rapidly in men than in women over the lifespan; systolic blood pressure rises in men and women, and diastolic blood pressure rises into the middle years in both men and women.
Hyperglycemia Impairs Blood Vessel Function
Robert Fried, Richard M. Carlton in Type 2 Diabetes, 2018
This chapter describes the steady process whereby oxidative stress leads to Type 2 diabetes, and damages vascular endothelium, by causing loss of nitric oxide (NO) synthesis. This loss results in both micro- and macrovessel damages as commonly seen in neuro- and vasculopathies present in many organs ranging from the eyes to the kidneys. The chapter also cites the evidence for endoplasmic reticulum, and mitochondrial stress in vasculopathies resulting from oxidative stress. Here also is a detailed discussion of various means of analysis permitting evaluation of damage due to diabetes. These include clinical correlates of arterial pulse waveform, and velocity, and flow-mediated vasodilation and reactive hyperemia.
Nitric Oxide and Nitric Oxide Synthase in the Kidney: Potential Roles in Normal Renal Function and in Renal Dysfunction
Published in Endothelium, 1995
Nathalie Hill-Kapturczak, Matthias H. Kapturczak, Tadeusz Malinski, Peter Gross
A detailed overview of nitric oxide and nitric oxide synthases in the kidney is presented. Physiologically, constitutive and inducible nitric oxide synthases have been detected in basically all vascular segments of the kidney, including all large vessels and arterioles that are primarily involved in the regulation of renal hemodynamics. It was observed that nitric oxide increases renal blood flow, decreases renal vascular resistance, and exerts variable effects on glomerular filtration rate depending on the experimental conditions. In addition, macula densa generated nitric oxide appears to mediate tubuloglomerular feedback. Constitutive and inducible nitric oxide synthases have also been delineated in most renal tubular segments. The inner medullary collecting duct was shown to contain the highest amount of constitutive nitric oxide synthase as compared to other nephron segments. It appears that nitric oxide may directly enhance tubular reabsorption in the collecting duct and the proximal tubule. Pressure-natriuresis, which may be a combination of both hemodynamic effects and an influence on tubular transport, may also be influenced directly and/or indirectly by nitric oxide. Due to its diverse functions, nitric oxide has been implicated in the pathophysiology of several renal diseases. Cyclosporin A toxicity, renal mass reduction, glomerular thrombosis, and ureteral obstruction, have all been found to be associated with diminished nitric oxide. On the other hand, incipient diabetes mellitus, ischemic acute renal failure, renal dysfunction of septic shock, advanced liver cirrhosis, and glomerulonephritis appear to be related to overabundant nitric oxide synthesis. Much has been learned regarding nitric oxide and the kidney, however, important questions remain to be clarified. Exciting new developments in nitric oxide research, including selective nitric oxide synthase inhibitors and alterations of the nitric oxide synthase gene(s), will add to the present understanding of nitric oxide. The kidney will probably turn out to be an organ amenable to some nitric oxide related therapeutic interventions.
Nitric oxide donor drugs: current status and future trends
Published in Expert Opinion on Investigational Drugs, 2002
Nitric oxide synthesised in endothelial cells that line blood vessels has a wide range of functions that are vital for maintaining a healthy cardiovascular system. Reduced nitric oxide availability is implicated in the initiation and progression of many cardiovascular diseases and delivery of supplementary nitric oxide to help prevent disease progression is an attractive therapeutic option. Nitric oxide donor drugs represent a useful means of systemic nitric oxide delivery and organic nitrates have been used for many years as effective therapies for symptomatic relief from angina. However, nitrates have limitations and a number of alternative nitric oxide donor classes have emerged since the discovery that nitric oxide is a crucial biological mediator. This review focuses on novel advances and possible future directions in nitric oxide donor drug development.
Air Pollution is Associated with Increased Level of Exhaled Nitric Oxide in Nonsmoking Healthy Subjects
Published in Archives of Environmental Health: An International Journal, 1999
Jan Van Amsterdam, Bert Verlaan, Henk Loveren, Bernhard Elzakker, Sjef Vos, Antoon Opperhuizen, Peter Steerenberg
The authors sought to determine which air pollutant is responsible for the increase in exhaled nitric oxide observed in healthy subjects. Exhaled nitric oxide was measured in 16 nonsmoking healthy subjects on 14 workdays, during which there were varying air-pollution levels. Contamination of samples by ambient nitric oxide was excluded. The baseline value of exhaled nitric oxide, determined at times when outdoor air pollution was low, ranged from 7 to 43 ppb (mean = 28 ± 5 ppb). The daily value of exhaled nitric oxide (range = 5–60 ppb) was associated positively with ambient carbon monoxide (r = .85) and nitric oxide (r = .81). Exposure during the morning hours to high levels of outdoor pollution was associated with increased exhaled nitric oxide (i.e., 50% above baseline), which persisted for up to 5 h (i.e., 32% above baseline). These results indicated that exhaled nitric oxide levels represent a useful biomonitor of individual exposure to air pollutants.