Enhanced endothelium-independent vasodilator response to calcitonin gene-related peptide in hypertensive rats

In isolated superior mesenteric arteries, vasodilation induced by calcitonin gene-related peptide (CGRP) was significantly larger in 12-week-old spontaneously hypertensive rats (SHR) than Wistar-Kyoto rats (WKY). In WKY and 6-week-old SHR, most of the vasodilator response to CGRP was abolished by Nw-nitro-L-arginine and indomethacin. In contrast, the inhibitors caused no significant change in the response in 12-week-old SHR. Vasodilations induced by acetylcholine and isoproterenol were smaller in 12-week-old SHR than WKY, and that induced by sodium nitroprusside was comparable in both tissues. These results suggest that endothelium-independent vasodilator activity of CGRP is enhanced in hypertensive SHR, which overwhelms the decreased endothelium-dependent effects.