CGRP-mediated changes in segmental resistances in the canine forelimb.

Abstract

Calcitonin gene-related peptide (CGRP) is a 37 amino acid peptide which is found in high concentrations in the perivascular nerves innervating the resistance vessels of the peripheral circulation. In the current study we have infused CGRP at three infusion rates (.01, .1 and 1.0 micrograms/min into the brachial artery for thirty minutes at each infusion rate) in the isolated, innervated canine forelimb perfused at natural flow. We measured large artery and vein pressures, small artery and vein pressures and blood flows in both the skin and skeletal muscle circulations for the calculation of total and segmental (large artery, small vessel and large vein) vascular resistances. Infusion of the lowest dosage of CGRP produced slight vasodilation in some animals but did not significantly alter the mean resistances of all the animals as a group. The middle dosage resulted in a 55% decrease in total forelimb resistance and a small but significant decrease in systemic arterial pressure. The highest dosage of CGRP resulted in a 65% decrease in total forelimb resistance and a 34% decrease in systemic arterial pressure. The decreases in forelimb resistances were equally distributed between skin and muscle and were manifested in both large artery and small vessel resistances. The potent vasodilatory effects of CGRP and its concentration in perivascular nerves innervating the resistance vessels of the peripheral circulation suggests a potential role for CGRP in control of circulatory function under normal and/or pathophysiological conditions.