Role of endothelium-derived nitric oxide in the regulation of blood pressure.

Abstract

The role of endothelium-derived nitric oxide in the regulation of blood pressure in the anesthetized rabbit was studied with Na-monomethyl-L-arginine (L-NMMA), a specific inhibitor of its formation from L-arginine. L-NMMA (3-100 mg-kg-'), but not its D-enantiomer, induced a dosedependent long-lasting (15-90 min) increase in mean systemic arterial blood pressure. L-NMMA (100 mg kg-') also inhibited significantly the hypotensive action of acetylcholine, without affecting that of glyceryl trinitrate. Both these actions of L-NMMA were reversed by L-arginine (300 mg-kg-'), but not by D-arginine (300 mg-kg-'), indomethacin (1 mg-kg-'), prazosin (0.3 mg-kg-'), or by vagotomy. The effects of L-NMMA in vivo were associated with a significant inhibition of the release of nitric oxide from perfused aortic segments ex vivo. This inhibition was reversed by infusing L-arginine through the aortic segments. These results indicate that nitric oxide formation from L-arginine by the vascular endothelium plays a role in the regulation of blood pressure and in the hypotensive actions of acetylcholine.Although endothelium-dependent vascular relaxation and the release of endothelium-derived relaxing factor in vitro has been clearly established (1-4), there is only circumstantial evidence to indicate their occurrence in vivo. Alterations in vessel diameter that follow changes in blood flow are endothelium dependent (5). Furthermore, damage to the endothelium (6, 7) or treatment with methylene blue (8) or gossypol (9), two nonspecific inhibitors of endothelium-dependent relaxation, all abolish the response to endothelium-dependent vasodilators in vivo without affecting the response to the endothelium-independent vasodilators, sodium nitroprusside or glyceryl trinitrate (n3Gro).Nitric oxide (NO) accounts for the biological actions of endothelium-derived relaxing factor (10-15) and is formed by vascular endothelial cells from the terminal guanido nitrogen atom(s) of the amino acid L-arginine (16,17). This biosynthetic process, the endothelium-dependent relaxation of vascular rings, and the vasodilatation induced by acetylcholine (ACh) in the coronary circulation of the rabbit heart are inhibited by the L-arginine analogue, Na-monomethyl-L-arginine . These results indicate that L-arginine is the physiological precursor for NO synthesis by the vascular endothelium.We have now used L-NMMA to investigate the role of NO in the regulation of blood pressure in the anesthetized rabbit.MATERIALS AND METHODS Methods. Male New Zealand White rabbits (2.0-2.2 kg) were anesthetized with sodium pentobarbitone (40-50 mg-kg-1). Anesthesia was then maintained by a continuous infusion of sodium pentobarbitone (15 mg kg-' hr-1) via the left marginal ear vein and the rabbits were ventilated with room air via a tracheotomy tube.

Tetrahydrobiopterin: a novel antihypertensive therapy

“…NO is a potent endothelium-derived vasodilator that regulates BP and regional blood flow. [1][2][3][4][5][6] A decrease in NO production or bioavailability reduces endothelium-dependent dilation and increases vascular tone. In addition, NO mediates many of the protective functions of the endothelium, including inhibition of vascular smooth muscle proliferation, platelet aggregation and expression of proinflammatory cytokines.…”

“…[1][2][3][4][5][6] Decreases in NO production or bioavailability impair endothelium-dependent dilation that can be both a consequence as well as a cause of hypertension. Among other protective roles of the endothelium, mediated in part by NO, are the inhibition of vascular smooth muscle cell proliferation and growth, and inhibition of proinflammatory cytokine expression, platelet aggregation and oxidative modification of low-density lipoprotein.…”

Effects of angiotensin converting enzyme inhibition on endothelial vasodilator function in primary human hypertension

“…The mechanism responsible for the vasodilator effect of acetylcholine has been mostly clarified and most of the activity of what has been termed endothelium-derived relaxing factor (EDRF) can be attributed to endothelial generation of nitric oxide or a substance that spontaneously generates nitric oxide' 4 ' from 1-arginine' 5 '. Moreover, it has become clear that basal release of EDRF, both in animal experiments' 6 ' 7 ' and healthy man' 8 ', is involved in the regulation of vascular tone. In addition to modulating vascular muscle tone, the endothelium appears to be a key element in the early phases of the development of atherosclerosis' 91 .…”

Cardiovascular effects induced by the hydroalcoholic extract of the stem of Xylopia cayennensis in rats

“…HEXC (5, 10, 20 and 30 mg/kg i.v., randomly) produced a dose-dependent hypotension associated with an increase in the heart rate. As endothelium-derived NO plays an important role in the regulation of blood pressure and vascular tone (Rees et al, 1989;Moncada et al, 1991) it is possible to assume that the decrease in blood pressure may be due to NO release from vascular endothelium. In the presence of NO-synthase inhibition (L-NAME 20 mg/Kg, i.v.…”