Y. Mimaki et al., INVOLVEMENT OF CALCITONIN-GENE-RELATED PEPTIDE (CGRP) RECEPTORS IN INSULIN-INDUCED VASODILATATION IN MESENTERIC RESISTANCE BLOOD-VESSELS OFRATS, British Journal of Pharmacology, 123(8), 1998, pp. 1684-1690
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.