Impaired muscarinic endothelium-dependent relaxation and cyclic guanosine 5'-monophosphate formation in atherosclerotic human coronary artery and rabbit aorta.

Abstract

The dependence of vascular relaxation on an intact endothelium and the relationship between relaxation and cyclic GMP accumulation were determined in coronary arteries isolated from cardiac transplantation patients with or without coronary atherosclerosis. In nonatherosclerotic arteries, the endothelium-dependent agent acetylcholine produced concentration-related relaxations. In atherosclerotic arteries, endothelium-dependent relaxations were abolished with acetylcholine, partly suppressed with substance P and histamine, and completely preserved with the ionophore A23187. In these arteries, the endothelium-independent agent nitroglycerin remained fully active. Accumulation of cyclic GMP in atherosclerotic strips was suppressed with acetylcholine but unattenuated with A23187 and nitroglycerin. In aortas from rabbits with diet-induced atherosclerosis, there was likewise an impaired cholinergic relaxation and cyclic GMP accumulation in the presence of preserved responses to A23187 and nitroglycerin. The results demonstrate that impaired cholinergic responses in atherosclerotic arteries reflect a muscarinic defect and not an inability of endothelium to release endothelial factor or smooth muscle to respond to it.

The effects of chronic phosphodiesterase-5 inhibitor use on different organ systems

“…[10][11][12][13] Rosano et al 63 noted that chronic therapy with tadalafil improved endothelial function in men with increased cardiovascular risk. In total, 32 patients were randomized to receive tadalafil 20 mg and placebo for 4 weeks.…”

“…Erectile dysfunction (ED) is a common medical condition linked both to endothelial dysfunction [1][2][3][4][5][6][7][8][9][10][11][12][13] as well as multiple other comorbid conditions. [14][15][16][17] Historically, the treatment for ED has been limited to a selected group of specialists, namely urologists and sexual therapists.…”

Why do patients with heart failure suffer from erectile dysfunction? A critical review and suggestions on how to approach this problem

“…34 Another hypothesis is that underlying atherosclerosis alters the L-arginine-NO pathway, decreasing NO production. [35][36][37][38] Oxygen-derived free radicals have also been associated with inhibition of Why do patients with heart failure suffer from ED? S Rastogi et al S27 endothelium-dependent vasodilation, suggesting that rapid inactivation of NO may be caused by increased free radical production.…”

Endothelial Regulation of Vascular Tone and Growth

“…66 Endothelium-independent re laxations to nitrovasodilators remain preserved, how ever, except in severely atherosclerotic arteries. 1 In human coronary arteries, atherosclerosis attenu ates endothelium-dependent relaxations to substance P, bradykinin, aggregating platelets, and calcium ionophore, 76 ' 77 and in vivo acetylcholine and serotonin cause paradoxical vasoconstriction. 78,79 The nature of the mechanism responsible for the marked impairment or loss of endothelium-dependent relaxations in atherosclerosis is controversial.…”