Urocortin reduces the viability of adult rat vascular smooth muscle cells via inhibiting L-type calcium channels.
The newly isolated peptide, urocortin (UCN), is a member of the corticotropin-releasing factor (CRF)-related peptides that has been found to have potent cardiovascular protective effects. In order to investigate the effect of UCN on the viability of adult rat vascular smooth muscle cells (VSMC) and the relevant mechanisms, we exposed the VSMC to UCN to observe the change in cell viability using MTT assay and intracellular calcium concentration using confocal laser scanning microscope methods. Our results showed that UCN (10(-7)M) inhibited the viability of VSMC by about 26% (P<0.05, compared to control). The effect was concentration-dependent, but it was not dependent on the affecting time. Glybenclamide (Gly, 10(-5)M), the ATP-sensitive potassium channel (K(ATP) channel) blocker, and astressin (10(-6)M), a competitive antagonist of CRF receptors, had no influence on this inhibition. Bay K8644 (10(-6)M), a special L-type calcium channel activator, increased the viability of VSMC. Pre-treatment of the cells with UCN diminished the effect of Bay K8644 (n=6, P<0.05). UCN was also observed to reduce the intracellular Ca2+ increase induced by KCl and Bay K8644. There was no significant difference in nitrite accumulation between UCN groups and the control. In conclusion, UCN reduced the viability of VSMC through L-type calcium channels. These interesting results might suggest that UCN may be a new vasoactive agent involved in hindering vascular remodeling in combination with previous reports about UCN's hypotensive effects.
Tao
Jin
J
Department of Pharmacology, Nanjing Medical University, Hanzhong Road 140, Nanjing 210029, PR China.
Chen
Jiandong
J
Wu
Yuqing
Y
Li
Shengnan
S
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000201:enzymology; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D054832:Urocortins
D020746:Calcium Channels, L-Type; D054832:Urocortins; D003346:Corticotropin-Releasing Hormone; D002118:Calcium