The relaxant effect of urocortin in rat pulmonary arteries.
Urocortin is a potent vasodilator, which plays physiological or pathophysiological roles in systemic circulation. However, little is known about its action on pulmonary circulation. The present study was aimed to characterize some cellular mechanisms underlying the relaxant effect of urocortin in isolated rat pulmonary arteries. Changes in isometric tension were measured on small vessel myographs. Urocortin inhibited U46619-induced contraction with reduction of the maximal response. Urocortin-induced relaxation was independent of the presence of endothelium. Inhibitors of nitric oxide (NO)-dependent dilator, NG-nitro-L-arginine methyl ester or 1H-[1,2,4]oxadizolo[4,3-a]quinoxalin-1-one, did not affect the relaxation. Astressin (100-500 nM), a corticotropin-releasing factor (CRF) receptor antagonist and KT5720, a protein kinase A (PKA) inhibitor reduced urocortin-induced relaxation. Urocortin produced less relaxant effect in 30 mM K+- than U46619-contracted arterial rings. Urocortin did not reduce CaCl2-induced contraction in 60 mM K+-containing solution. Ba2+ (100-500 microM) but not other K+ channel blockers reduced the relaxant responses to urocortin. Urocortin also relaxed the rings preconstricted by phorbol 12,13-diacetae in normal Krebs solution while this relaxation was less in a Ca2+-free solution. Our results show that urocortin relaxed rat pulmonary arteries via CRF receptor-mediated and PKA-dependent but endothelium/NO or voltage-gated Ca2+ channel-independent mechanisms. Stimulation of Ba2+-sensitive K+ channel may contribute to urocortin-induced relaxation. Finally, urocortin relaxed pulmonary arteries partly via inhibition of a PKC-dependent contractile mechanism.
Chan
Y C
YC
Department of Physiology, Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
Yao
X Q
XQ
Lau
C W
CW
Chan
F L
FL
He
G W
GW
Bourreau
J-P
JP
Huang
Y
Y
D000818:Animals; D017609:Barium Compounds / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D004727:Endothelium / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D054832:Urocortins
D017609:Barium Compounds; D002227:Carbazoles; D002712:Chlorides; D007211:Indoles; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011758:Pyrroles; D054832:Urocortins; C024986:barium chloride; D009569:Nitric Oxide; C057416:KT 5720; D003346:Corticotropin-Releasing Hormone; D011493:Protein Kinase C