(1) NO relaxes vascular smooth muscle cells. NO is released from the endothelium in response to pulsatile stretch and flow-induced shear stress. When flow to a tissue is suddenly increased by arteriolar dilation, the large arteries to the tissue also dilate. This flow-induced dilation is due to local release of NO.
Moreover, any luminal narrowing of arterial vessels increases the local blood flow velocity, which stimulates NO release and results in post-steno tic vasodilatation. Flow-induced vasodilatation also occurs during physical exercise. Exercise- induced NO formation may explain the beneficial effects of endurance training on the cardiovascular system.
(2) NO release is brought about by both vasoconstrictor and vasodilator substances. The vasoconstrictors that act directly on vascular smooth muscle would produce much greater constriction if they did not simultaneously cause the release of NO. Conversely, the vasodilators that have direct actions on vascular smooth muscle produce greater vasodilatation by triggering the simultaneous release of NO. Many of these substances are released during platelet aggregation and blood coagulation. Hence, aggregating platelets cause vasodilatation if the endothelium is healthy and vasoconstriction if the arteries are atherosclerotic.
(3) There is a balance in blood between endothelium-derived vasoconstrictors like endothelins and vasodilators like NO. Hence, a constant release of NO is necessary to maintain normal blood pressure and NO deficiency can cause clinical hypertension. The drug nitroglycerin, which is of great value in the treatment of angina, exerts its vasodilator effects by being converted to NO.
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(4) Penile erection is produced by release of NO, with consequent vasodilatation and engorgement of the corpora cavernosa. The drug Viagra® (Sildenafil), a selective inhibitor of cGMP-specific phosphodiesterase, acts by inhibiting the inactivation of NO.
(5) NO inhibits platelet adhesion and aggregation. This effect, together with its vasodilator effect, is extremely important for the maintenance of the normal flow of blood.
(6) NO decreases LDL oxidation and inhibits super oxide anion production by inhibiting NADPH reductase activity. These actions are related to the strong anti-atherosclerotic effect exerted by NO.
(7) NO is a mediator of the inflammatory response. It is necessary for the cytotoxic activity of macrophages, including their ability to kill cancer cells. Production of NO is elevated in inflammatory diseases.