Difference in the characteristics of ETA-receptor-stimulated response between rat small pulmonary and renal arteries.
We investigated the difference in the characteristics of endothelin-1 (ET-1)-induced contraction and the responses of intracellular Ca(2+) concentration ([Ca(2+)](i)) between rat small pulmonary artery and renal artery. ET-1 (30 nM) failed to elicit any contraction in renal arteries pretreated with 3 microM BQ-123, an ETA blocker. However, in the pulmonary artery a combination of BQ-123 and BQ-788, an ETB blocker (5 microM each), only partially inhibited the ET-1-induced contraction (by 25%). To focus on the ETA receptor, in the presence of 5 microM BQ-788, nitric oxide donors (sodium nitroprusside and (+/-)-S-nitroso-N-acetylpenicillamine) and forskolin reduced both the ET-1-induced contraction and increase in [Ca(2+)](i) in both pulmonary and renal arteries. However, the effects were stronger in the renal than in the pulmonary artery. ET-1-induced increase in [Ca(2+)](i) was only partially attenuated by 10 microM verapamil (to 81% of control) in pulmonary arteries but was reduced to 56.1% of control in renal arteries. Our results provide evidence that ET-1 may activate ET receptor(s) insensitive to both BQ-123 and BQ-788 in rat small pulmonary artery, at least under these conditions. Furthermore, the effects of relaxants such as L-type Ca(2+) channel blocker and nitric oxide donors on the ET-1-induced contraction were studied.
Kato
Kenichi
K
Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Sawara, Japan. kenkato@med.gunma-u.ac.jp
Betts
Luisa C
LC
Kozlowski
Roland Z
RZ
Kitamura
Kenji
K
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D019332:Endothelin-1 / Q000494:pharmacology*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A / Q000502:physiology*; D012077:Renal Artery / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*
D002121:Calcium Channel Blockers; D019332:Endothelin-1; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; D005576:Colforsin; C086539:BQ 788; D000242:Cyclic AMP; C072247:cyclo(Trp-Asp-Pro-Val-Leu)