Role of Nitric Oxide in the Cardiovascular and Renal Systems

Abstract

The gasotransmitters are a family of gaseous signaling molecules which are produced endogenously and act at specific receptors to play imperative roles in physiologic and pathophysiologic processes. As a well-known gasotransmitter along with hydrogen sulfide and carbon monoxide, nitric oxide (NO) has earned repute as a potent vasodilator also known as endothelium-derived vasorelaxant factor (EDRF). NO has been studied in greater detail, from its synthesis and mechanism of action to its physiologic, pathologic, and pharmacologic roles in different disease states. Different animal models have been applied to investigate the beneficial effects of NO as an antihypertensive, renoprotective, and antihypertrophic agent. NO and its interaction with different systems like the renin⁻angiotensin system, sympathetic nervous system, and other gaseous transmitters like hydrogen sulfide are also well studied. However, links that appear to exist between the endocannabinoid (EC) and NO systems remain to be fully explored. Experimental approaches using modulators of its synthesis including substrate, donors, and inhibitors of the synthesis of NO will be useful for establishing the relationship between the NO and EC systems in the cardiovascular and renal systems. Being a potent vasodilator, NO may be unique among therapeutic options for management of hypertension and resulting renal disease and left ventricular hypertrophy. Inclusion of NO modulators in clinical practice may be useful not only as curatives for particular diseases but also for arresting disease prognoses through its interactions with other systems.

Keywords: angiotensin II; hypertension; kidney disease; nitric oxide; noradrenaline; vasodilation.

Figure 1

Synthesis of nitric oxide from precursor l-arginine in endothelial cells and mechanism of vasodilation in vascular smooth muscle.

Figure 2

Different levels of NO and Ang II depicting different states of the body. (A) shows normal levels of NO and Ang II in normal physiological conditions. (B) represents that levels of Ang II increased while that of NO is reduced in plasma and tissue in pathological states like hypertension and LVH, while (C) indicates that pharmacological treatment with NO donors or Ang II inhibitors increases the NO and reduced the levels of Ang II to offset the pathological state.

Figure 3

Overall summary of interactions described between H₂S and NO in living system.

Figure 4

Interactions of NO with different systems and modulation of their functions in cardiovascular and renovascular systems.