Endothelin-1-induced constriction inhibits nitric-oxide-mediated dilation in isolated rat resistance arteries.
Vascular endothelial cells release dilatory compounds like nitric oxide and prostacyclin, as well as contractile factors like endothelin-1 (ET-1). We investigated the interaction of ET-1 with nitric-oxide-mediated dilation in cannulated pressurized (75 mm Hg) arterioles from rat cremaster muscle (180 +/- 3 microm). Arterioles constricted spontaneously to 101 +/- 3 microm, while ET-1 (0.4 nM) increased constriction to 78 +/- 3 microm. Acetylcholine, an endothelium-dependent nitric-oxide-mediated vasodilator induced a dose-dependent dilation during spontaneous tone. After addition of ET-1, the response to acetylcholine was significantly impaired. Nitroprusside, an endothelium-independent nitric oxide donor, induced a dose-dependent dilation that was almost completely inhibited by ET-1. In contrast, 8-Br-cGMP-induced dilation was unaffected. Thus, ET-1 appears to inhibit nitric-oxide-mediated dilation at the level of cGMP formation or degradation. The effect of ET-1 appears to be specific for nitric oxide as responses to a prostacyclin analogue were impaired at low doses only. The inhibitory effect of ET-1 on nitric-oxide-mediated dilation could be mimicked with high potassium (65 +/- 6 microm), but not with phenylephrine (74 +/- 8 microm)-induced constriction. These data show a direct inhibitory effect of ET-1 on nitric-oxide-mediated dilation in isolated skeletal muscle arterioles.
Bakker
E N
EN
Laboratory for Physiology, Vrije Universiteit, Amsterdam, The Netherlands.
van der Linden
P J
PJ
Sipkema
P
P
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply; D009569:Nitric Oxide / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014655:Vascular Resistance / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D019332:Endothelin-1; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D011188:Potassium