Some Peculiar Effects of NO-Synthase Inhibition on the Structure and Function of Cardiovascular System

Frantisek      Kristek

doi:10.2174/138920111798281072

Abstract

Long-term increase of blood pressure represents one of the most important risk factors triggering many cardiovascular diseases, and via counter-regulatory mechanisms it is itself modulated by them. Adequate perfusion of the respective areas with nutrients requires appropriate production of vasodilatory and vasoconstrictory agents. Disharmony among them has an important impact on mechanical properties of the arteries, resulting in pathological alterations in the cardiovascular system. Defective production of the vasodilatory agent nitric oxide (NO) has a pronounced effect on this delicate balance and can evoke functional and structural changes in the cardiovascular system leading to hypertension. This review is focused mainly on changes in the cardiovascular system of newborn and adult Wistar rats after long-term administration of two different types of NO-synthase inhibitors: nonspecific inhibitor NG-nitro-L-arginine methylester and specific inhibitor of neuronal NO-synthase 7-nitroindazole. A possible supplementation of decreased endogenous NO production by NO donors is discussed. Particular attention is given to the complex interplay among blood pressure, arterial geometry, including arterial wall thickness, cross-sectional area, inner diameter, and individual components of the arterial wall, as extracellular matrix, endothelial and smooth muscle cell trophicity. Some methodological remarks for determination of the arterial geometry are also presented. Better understanding of the interrelationship among the factors involved can help in explaining more accurately differences in functional manifestations of vessels in various types of hypertension. The review indicates that the current concept of NO production, effect of NO deficiency, substitution of the missing NO in failing NO production in the cardiovascular system appears to be oversimplified.

Keywords: Artery, nitric oxide, regulation, structure, cardiovascular diseases, extracellular matrix, arterial geometry, synthase inhibition, myocardium, cardiac hypertrophy, angiogenesis, cardiovascular hypertrophy, muscle cells, acetylcholine, semi-essential amino acid