Role of corticotropin-releasing factor receptor type 2 beta in urocortin-induced vasodilation of rat aortas.
Urocortin has a high affinity for the corticotropin-releasing factor receptor type 2beta (CRF-R2beta). This study was conducted to reveal the role of CRF-R2beta in blood vessels. CRF-R2beta expressions were detected both in smooth muscle and endothelium from Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) aortas, and there was no significant difference between them. Urocortin reduced phenylephrine-induced contraction of aorta with endothelium dose-dependently in both rats. However, deendothelialization significantly but not completely (about 50%) reduced the vasodilation. The reduction of vasodilatory action of urocortin by deendothelialization was age-dependent in SHR. An adenylyl cyclase inhibitor, SQ22536, significantly inhibited urocortin-induced relaxation in denuded WKY and SHR aortas, while in preparations with endothelium, neither SQ22536 nor L-NMMA reduced the relaxation. However, simultaneous addition of both drugs significantly reduced the relaxation. In contrast to young rats (7-week-old), in aged rats (19-week-old), L-NMMA successfully reduced urocortin-induced relaxation of aorta with endothelium. These results suggest that urocortin relaxes aorta at least partly via two signal pathways, that is, an increase in intracellular cAMP by binding to CRF-R2beta expressed in smooth muscle cells and NO production from endothelium evoked by binding to the receptors expressed in endothelium and that aging increases the role of the latter system.
Department of Pharmacology, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
Izumi
I
Miki
Kazuhiko
K
Seya
Shigeru
S
Motomura
Ken-Ichi
K
Furukawa
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018019:Receptors, Corticotropin-Releasing Hormone / Q000502:physiology*; D013045:Species Specificity; D054832:Urocortins; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
C101531:CRF receptor type 2; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D003346:Corticotropin-Releasing Hormone