INVOLVEMENT OF CALCITONIN-GENE-RELATED PEPTIDE (CGRP) RECEPTORS IN INSULIN-INDUCED VASODILATATION IN MESENTERIC RESISTANCE BLOOD-VESSELS OFRATS

1 The vascular effect of insulin in the mesenteric resistance blood ve ssel and the role of calcitonin gene-related peptide (CGRP)-receptor i n insulin-induced vascular responsiveness were investigated in rats. 2 The mesenteric vascular beds isolated from Wistar rats were perfused with Krebs solution, and perfusion pressure was measured with a pressu re transducer. In preparations contracted by perfusion with Krebs solu tion containing methoxamine in the presence of guanethidine, the perfu sion of insulin (from 0.1 to 3000 nM) caused a concentration-dependent decrease in perfusion pressure due to vasodilatation. The pD(2) value and maximum relaxation (%) were 6.94+/-0.22 and 43.9+/-5.2, respectiv ely. 3 This vasodilator response to insulin was unaffected by 100 nM p ropranolol (beta-adrenoceptor antagonist) plus 100 nM atropine (muscar inic cholinoceptor antagonist), 100 mu M L-N-G-nitroarginine (nitric o xide synthase inhibitor), 1 mu M ouabain (Na+-K+ ATPase inhibitor), or 1 mu M glibenclamide (ATP sensitive K+-channel inhibitor). 4 In prepa rations without endothelium, perfusion of insulin produced a marked va sodilatation. The pD(2) value and maximum relaxation (%) were 7.62+/-0 .21 and 81.0+/-4.6, respectively, significantly greater than in prepar ations with intact endothelium. 5 The vasodilator responses to insulin in the preparations without endothelium were significantly inhibited by CGRP[8-37], a CGRP receptor antagonist, whereas pretreatment with c apsaisin, a toxin for CGRP-containing nerves, did not affect insulin-i nduced vasodilatation. 6 These results suggest that insulin induces no n-adrenergic, non-cholinergic and endothelium-independent vasodilatati on, which is partially mediated by CGRP receptors.