Sildena®l (0.1 ± 30 mM), a cyclic GMP phosphodiesterase 5 (PDE 5) inhibitor, induced inhibition of electrically evoked contractions of ring segments of human vas deferens from 34 vasectomies. Zaprinast (0.1 ± 100 mM), another PDE 5 inhibitor, and the nitric oxide (NO) donor sodium nitroprusside (SNP) (0.1 ± 100 mM) had no e ect on neurogenic contractions. The inhibition induced by sildena®l was not modi®ed by the inhibitor of guanylate cyclase 1H-[1,2,4]oxadiazolo [4,3-a] quinoxaline-1-one (ODQ) (1 ± 30 mM) but it was abolished by the K + channel blockers tetraethylammonium (TEA, 1 mM), iberiotoxin (0.1 mM) and charybdotoxin (0.1 mM). Sildena®l, zaprinast and SNP did not a ect the contractions induced by noradrenaline. SNP (10 mM) caused elevation of cyclic GMP levels that was potentiated by sildena®l (10 mM) and zaprinast (100 mM). ODQ (10 mM) inhibited the increase in cyclic GMP. Sildena®l inhibits adrenergic neurotransmission in human vas deferens. The inhibition is not related to accumulation of cyclic GMP but is probably due to activation of prejunctional large-conductance Ca 2+ -activated K + channels.
The effects of deamino-8-D-arginine vasopressin (desmopressin), a V 2 receptor antidiuretic agonist, were studied in isolated rings from branches of renal arteries obtained from 22 patients undergoing nephrectomy. The rings were suspended in organ bath chambers for isometric recording of tension. In precontracted rings with norepinephrine (10 ؊6 to 3 ؋ 10 ؊6 mol/L), desmopressin (10 ؊11 to 3 ؋ 10 ؊7 mol/L) caused endothelium-dependent relaxation (81% ؎ 4% reversal of the initial contraction in arteries with endothelium; 20% ؎ 4% in arteries without endothelium; P < . A rginine vasopressin promotes reabsorption of water in renal tubular cells through V 2 receptors coupled to adenylate cyclase activation and acts directly on human vascular smooth muscle to produce constriction through V 1 receptor stimulation.1-4 The specific V 2 receptor agonist deamino-8-d-arginine vasopressin (desmopressin) is a synthetic analogue of the natural hormone vasopressin with a strong V 2 antidiuretic effect and minimal V 1 pressor activity.5 Extrarenal actions of desmopressin include coagulation responses such as the release of factor VIIIc and von Willebrand factor, 6 -8 and cardiovascular effects such as increase in heart rate, decrease in mean arterial blood pressure, facial flushing, and increase in forearm blood flow. 9 -11 Whether these effects are mediated by receptors is not clearly established, but studies in humans demonstrate that an extrarenal V 2 receptor could be responsible for the coagulation and hemodynamic responses to desmopressin. 10 -12 Experiments in isolated arteries show that desmopressin induces concentration-dependent relaxation in human cerebral and mesenteric arteries that is prevented by the mixed V 1 -V 2 receptor antagonist desGly-d(CH 2 ) 5 -d-Tyr(Et)ValAVP but not
The results demonstrate that L-NMMA and ADMA reduce basal and stimulated nitric oxide activity in human renal arteries. An increase in the plasma concentrations of methylarginines associated with renal disease should be considered as a risk factor for endothelial dysfunction and abnormal vasomotor tone in human renal arteries.
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