Pharmacological characterization of endothelin-induced rat pulmonary arterial dilatation.
1. The aim of study was to characterize endothelin (ET)-induced vasodilation in isolated extrapulmonary rat arteries (EPA) and in intrapulmonary arteries (IPA) preconstricted with 1 microM phenylephrine. 2. The ET-3 (1 nM-100 nM)- and ET-1 (10 nM-100 nM)-induced transient vasodilatations in EPA were more potent than those in IPA. The vasodilatation induced by ET-3 (100 nM) was larger than that induced by ET-1 (100 nM). 3. Both the ETB antagonist, BQ788 (3 microM) and or endothelium denudation, but not the ETA antagonist, BQ123 (3 microM), abolished the vasodilation induced by ET-1 or ET-3 (100 nM each) in EPA and in IPA. The ATP-sensitive K + channel blocker, glibenclamide (20 microM) and the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA, 1 mM) suppressed the ET-induced vasodilatation in EPA and in IPA. 4. We conclude that the vasodilatation induced by endothelins is markedly reduced in rat isolated IPA, and suggest that the endothelial ETB-mediated vasodilatation varies depending on rat pulmonary arterial regions. Furthermore, ETB-mediated vasodilatation involves activation of ATP-sensitive K+ channels and of nitric oxide synthase in rat isolated EPA and IPA.
Higashi
T
T
Third Department of Internal Medicine, Fukui Medical School, Japan.
Ishizaki
T
T
Shigemori
K
K
Yamamura
T
T
Nakai
T
T
D000818:Animals; D019332:Endothelin-1 / Q000494:pharmacology*; D019334:Endothelin-3 / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D015221:Potassium Channels; D011651:Pulmonary Artery / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D019332:Endothelin-1; D019334:Endothelin-3; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D015221:Potassium Channels; D019323:omega-N-Methylarginine; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu)