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

Abstract

1. 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.

2. 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.

3. This vasodilator response to insulin was unaffected by 100 nM propranolol (β-adrenoceptor antagonist) plus 100 nM atropine (muscarinic cholinoceptor antagonist), 100 μM L-N^G-nitroarginine (nitric oxide synthase inhibitor), 1 μM ouabain (Na⁺-K⁺ ATPase inhibitor), or 1 μM glibenclamide (ATP sensitive K⁺-channel inhibitor).

4. 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.

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 capsaisin, a toxin for CGRP-containing nerves, did not affect insulin-induced vasodilatation.

6. These results suggest that insulin induces non-adrenergic, non-cholinergic and endothelium-independent vasodilatation, which is partially mediated by CGRP receptors.

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