Endothelium-independent vasodilator effect of 2-nitro-1-phenyl-1-propanol on mesenteric resistance vessels in rats

Abstract

2-Nitro-1-phenyl-1-propanol (NPP) is a nitro alcohol with vasodilator activity in the rat aorta. The present study investigated the vasodilator properties of NPP in small vessels of the mesenteric bed, which, contrary to the aorta, contains resistance vessels. Using myography, isometric contractions were recorded in rings of second- and third-order branches from the rat mesenteric artery. NPP relaxed mesenteric ring preparations that were contracted with phenylephrine, U-46619, and KCl (40mM), resulting in significantly different EC50 values (0.41μM [0.31–0.55μM], 0.16μM [0.10–0.24μM], and 4.50μM [1.86–10.81μM], respectively). NPP-induced vasodilation decreased as the extracellular K+ concentration increased. The pharmacological blockade of K+ channels with tetraethylammonium, BaCl2, CsCl, and apamin also blunted NPP-induced vasorelaxation. In contrast, NPP-induced vasodilation was resistant to indomethacin, L-NG-nitroarginine methyl ester (L-NAME), and endothelium removal, indicating that neither prostaglandins nor the endothelial release of nitric oxide is involved in the relaxant effects of NPP. Conversely, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), cis-N-(2-phenylcyclopentyl)-azacyclotridec-1-en-2-amine hydrochloride (MDL-12,330A), and H-89 reduced NPP-induced vasodilation. Under Ca2+-free conditions, NPP did not alter transient contractions that were evoked by caffeine, but it reduced transient contractions that were evoked by phenylephrine. In mesenteric rings that were loaded with the fluorescent Ca2+ indicator Fluo-4 AM and stimulated with phenylephrine, NPP blunted both contractions and fluorescence signals that were related to cytosolic Ca2+ levels. In conclusion, the vasodilatory actions NPP on mesenteric vessel resistance involved the participation of cyclic nucleotides and the opening of K+ channels.