Nickel inhibits urocortin-induced relaxation in the rat pulmonary artery.
Urocortin relaxes rat pulmonary arteries partly through a cyclic AMP-dependent but Ca(2+) channel-independent mechanism. However, other participating mechanisms are relatively unknown. The present study was designed to examine whether the forward mode of Na(+)-Ca(2+) exchangers play a role in the relaxant responses to urocortin in isolated rat small pulmonary arteries. Endothelium-denuded rings were mounted on small vessel myographs for measurement of changes in isometric tension. Urocortin inhibited 9,11-dideoxy-11alpha,9alpha-epoxy-methanoprostaglandin F(2alpha) (U46619)-induced contraction in a concentration-dependent manner and this inhibition was reversed by astressin, a corticotropin-releasing factor receptor antagonist. Micromolar concentrations of nickel (Ni(2+)) chloride, a putative inhibitor of the Na(+)-Ca(2+) exchanger, reduced the relaxant responses to urocortin. Urocortin-induced relaxation was abolished in a Na(+)-free solution, a condition that eliminates influence of the forward mode of Na(+)-Ca(2+) exchanger. In contrast, the relaxant responses to atrial natriuretic peptide or forskolin were unaffected by Ni(2+) or with removal of extracellular Na(+). The present results provide indirect evidence suggesting that stimulation of Na(+)-Ca(2+) exchangers may contribute to urocortin-induced endothelium-independent pulmonary artery relaxation.
Lau
Chi-Wai
CW
Department of Physiology, Faculty of Medicine, Chinese University of Hong Kong, Shatin NT, China.
Chan
Yau Chi
YC
Yao
Xiaoqiang
X
Chan
Franky Leung
FL
Chen
Zhen-Yu
ZY
Huang
Yu
Y
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009532:Nickel / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors; D054832:Urocortins; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D019831:Sodium-Calcium Exchanger; D054832:Urocortins; D014662:Vasoconstrictor Agents; D005576:Colforsin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D009532:Nickel; D009320:Atrial Natriuretic Factor; D003346:Corticotropin-Releasing Hormone; D011188:Potassium