Urocortin II inhibits the apoptosis of mesenteric arterial smooth muscle cells via L-type calcium channels in spontaneously hypertensive rats.
Urocortin (UCN) II, a newly isolated corticotropinreleasing- factor (CRF) related peptide, has been found to have potent cardiovascular protective effects. To investigate the mechanisms of its vascular protective effects, we exposed mesenteric arterial smooth muscle cells (MASMC) from spontaneously hypertensive rats (SHR) to UCN II to observe the change in cell apoptosis using TUNEL assay and measured intracellular calcium concentration ([Ca2+]i) using confocal laser scanning microscope. In addition, effects of UCN II on L-type calcium currents (ICa,L) were also measured using whole-cell patch clamp. Our results showed that UCN II concentration-dependently, but time-independently inhibited cell apoptosis. Astressin 2B, a special CRF 2 receptor antagonist, had no influence on this inhibition. Hypoxia or Bay K8644, the L-type calcium channel activator, induced the apoptosis of MASMC from SHR. Pretreatment of the cells with UCN II diminished the effects of hypoxia or Bay K8644. UCN II was also observed to reduce [Ca2+]i increase induced by KCl or Bay K8644. UCN II concentration-dependently inhibited ICa,L, which was not affected by astressin 2B. It did not affect the activation of ICa,L, but markedly shifted the inactivation curve to the left. In conclusion, UCN II inhibits the apoptosis of MASMC from SHR via inhibiting L-type calcium channels.
Department of Pharmacology, Nanjing Medical University, Nanjing, China.
Jin
J
Tao
Yuan
Y
Zhang
Tuck Wah
TW
Soong
Shengnan
S
Li
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000032:analysis; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D015687:Cell Hypoxia; D002460:Cell Line; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008643:Mesentery / Q000098:blood supply*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D009569:Nitric Oxide / Q000032:analysis; D018408:Patch-Clamp Techniques; D051381:Rats; D011918:Rats, Inbred SHR; D054832:Urocortins
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D054832:Urocortins; D009569:Nitric Oxide; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D003346:Corticotropin-Releasing Hormone; D009543:Nifedipine; D002118:Calcium