Effects of calcitonin gene-related peptide (CGRP) on regional haemodynamics and on selected hepato-splanchnic arteries from the rat: A comparison with VIP and atriopeptin II

Abstract

The neuropeptides calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) were compared with atriopeptin II (AP II) for vasodilatory responses in the rat. The haemodynamic changes following intravenous infusion of non-hypotensive doses were measured by the microsphere technique. Isolated segments of arteries from the hepato-splanchnic region were assayed for tension responses. CGRP (2.9 pmol kg-1 min-1) caused significant reductions in vascular resistances in the spleen, the stomach and the myocardium. VIP was without detectable effects at a similar dose. At a 10-times higher dose, AP II was still without hypotensive effect and vascular resistance was reduced only in the submaxillary gland. CGRP, VIP and AP II produced endothelium-independent relaxations of isolated segments of the left gastric artery, the splenic artery and the hepatic artery. In the superior mesenteric artery (SMA) the response to CGRP was reduced by 90% after the endothelium was disrupted. When a functional endothelium was present, the potencies for CGRP were higher in the gastric artery, the splenic artery and the SMA than in the hepatic artery. The orders of potencies for the peptides were, for the gastric artery and the SMA CGRP greater than AP II greater than VIP, and for the splenic artery and the hepatic artery CGRP = AP II greater than VIP. In conclusion, vasodilations in the spleen and the stomach occurred only in response to infusion of CGRP. Consistently, significantly higher potency values were found for CGRP than for VIP in isolated arteries from these organs. However, there were examples of discrepancies between the in vitro and the in vivo responses to CGRP and AP II.