Involvement of calcitonin gene-related peptide (CGRP) receptors in insulin-induced vasodilatation in mesenteric resistance blood vessels of rats

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Abstract
The vascular effect of insulin in the mesenteric resistance blood vessel and the role of calcitonin gene‐related peptide (CGRP)‐receptor in insulin‐induced vascular responsiveness were investigated in rats. The mesenteric vascular beds isolated from Wistar rats were perfused with Krebs solution, and perfusion pressure was measured with a pressure transducer. In preparations contracted by perfusion with Krebs solution containing methoxamine in the presence of guanethidine, the perfusion of insulin (from 0.1 to 3000 nM) caused a concentration‐dependent decrease in perfusion pressure due to vasodilatation. The pD2 value and maximum relaxation (%) were 6.94±0.22 and 43.9±5.2, respectively. This vasodilator response to insulin was unaffected by 100 nM propranolol (β‐adrenoceptor antagonist) plus 100 nM atropine (muscarinic cholinoceptor antagonist), 100 μM L‐NG‐nitroarginine (nitric oxide synthase inhibitor), 1 μM ouabain (Na+‐K+ ATPase inhibitor), or 1 μM glibenclamide (ATP sensitive K+‐channel inhibitor). In preparations without endothelium, perfusion of insulin produced a marked vasodilatation. The pD2 value and maximum relaxation (%) were 7.62±0.21 and 81.0±4.6, respectively, significantly greater than in preparations with intact endothelium. The vasodilator responses to insulin in the preparations without endothelium were significantly inhibited by CGRP[8–37], a CGRP receptor antagonist, whereas pretreatment with capsaisin, a toxin for CGRP‐containing nerves, did not affect insulin‐induced vasodilatation. These results suggest that insulin induces non‐adrenergic, non‐cholinergic and endothelium‐independent vasodilatation, which is partially mediated by CGRP receptors. British Journal of Pharmacology (1998) 123, 1684–1690; doi:10.1038/sj.bjp.0701779