Mechanisms involved in the effects of endothelin-1 in pig prostatic small arteries

Abstract

Since endothelin-1 (ET-1) is involved in prostatic disorders, the current study investigated the mechanisms underlying the ET-1-induced effects in pig prostatic small arteries. The experiments were performed in rings mounted in microvascular myographs containing physiological saline solution at 37 oC for isometric force recordings. On basal tension, ET-1 (0.1–30 nM) evoked concentration-dependent contractions, which were enhanced by endothelium removal. ET-1 contractions were inhibited by blockade of endothelin ET A and ET B receptors, extracellular Ca 2+ removal and blockade of voltage-dependent (L-type)- and non-voltage-dependent-Ca 2+ channels. On endothelium intact rings precontracted with noradrenaline, the ET B endothelin receptor agonist BQ3020 promoted a concentration-dependent relaxation which was reduced by blockade of ET B receptors, nitric oxide synthase, guanylyl cyclase and prostanoids synthesis. Endothelium removal abolished its relaxant response and unmasked a BQ3020-induced contraction. Tetraethylammonium and 4-aminopyridine, blockers of non-selective K + channels and voltage-dependent K + (Kv) channels, respectively, inhibited the relaxations to BQ3020. Iberiotoxin, apamin and glibenclamide, blockers of large and small Ca 2+-activated- and ATP-dependent- K + channels, respectively, failed to modify these responses. These data suggest that ET-1 promotes contraction of pig prostatic small arteries by activating vascular smooth muscle contractile endothelin ET A and ET B receptors coupled to extracellular Ca 2+ entry, via voltage-dependent (L-type)- and non-voltage-dependent Ca 2+ channels, also being due to intracellular Ca 2+ mobilization. In addition, a population of endothelial ET B receptors mediates vasorelaxation via NO-cGMP pathway, vasodilator cyclooxygenase product(s) and Kv channels.