THE INVOLVEMENT OF CGRP IN ACETYLCHOLINE-INDUCED VASCULAR RELAXATION

Earlier work on peptidergic fibres suggested some involvement of CGRP perivascular nerve fibres in acetylcholine-induced endothelium-depende nt vascular relaxation. We have investigated the effect of blocking CG RP receptors and CGRP replacement on acetylcholine-induced endothelium -dependent vascular relaxation in the isolated perfused mesenteric art erial bed in normal Sprague-Dawley rats and in rats seven days followi ng freeze-denervation of the superior mesenteric artery. Freeze-denerv ation was carried out under pentobarbital anesthesia (40 mg/Kg). It wa s found that the ability of acetylcholine to cause relaxation was redu ced by CGRP receptor blocking with CGRP8-37 in vessels from control ra ts, but returned to pre-blocking levels after washout of the antagonis t. Treatment with CGRP increased the relaxation due to acetylcholine i n denervated vessel beds, but not in control tissues. The CGRP recepto r appears to be involved in the acetylcholine-induced relaxation of bl ood vessels. The mechanism of action is not known, although both acety lcholine and CGRP, act through activation of K+ channels, and CGRP may facilitate the activation of K+ channels by acetylcholine.