Systemic and regional hemodynamic effects of calcitonin gene-related peptide.

Abstract

Calcitonin gene-related peptide, a 37-amino-acid neuropeptide, has been shown to be widely distributed in periadventitial nerves throughout the cardiovascular system, particularly in association with coronary arteries. In vivo and in vitro studies have demonstrated that calcitonin gene-related peptide possesses potent vasodilator properties. Circulating calcitonin gene-related peptide is derived primarily from periadventitial nerves, though its systemic and regional hemodynamic effects are unknown. In this study, systemic and regional hemodynamics were determined by the radioactive microsphere technique prior to and following the intravenous administration of 65-pmol and 2.2-nmol doses of calcitonin gene-related peptide and vehicle to three groups of conscious, unrestrained rats. Vehicle administration did not change any systemic or regional organ hemodynamic parameter determined. In contrast, 65 pmol and 2.2 nmol of calcitonin gene-related peptide significantly decreased mean blood pressure and total peripheral resistance and increased heart rate in a dose-dependent manner, while only slightly increasing cardiac output. Both 65-pmol and 2.2-nmol doses of calcitonin gene-related peptide significantly increased blood flow (percentage of cardiac output) to the heart. There was no difference in blood flow to the heart between the two doses. In addition, the 2.2-nmol dose of calcitonin gene-related peptide significantly increased blood flow to the stomach, liver, and skin and decreased it to the brain, kidneys, and spleen. In conclusion, calcitonin gene-related peptide infusion decreases blood pressure in a dose-dependent manner primarily by peripheral vasodilation. In addition, calcitonin gene-related peptide selectively changes regional organ blood flow, particularly to cause coronary vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)

The paradoxical vascular interactions between endothelin‐1 and calcitonin gene‐related peptide in the rat gastric mucosal microcirculation

“…It will therefore be necessary in future studies to determine if this mucosal vasodilatation or any mediator release is a direct effect of ET-1 in the gastric microcirculation, perhaps through activation of ETB or other ET receptors (Masaki et al, 1991) or if it occurs secondarily to microvascular injury induced by Local intra-arterial infusion of a-CGRP induced a significant increase in gastric mucosal LDF. This agrees with previous reports where a-CGRP was found to be a potent vasodilator in the gastric microcirculation, determined by use of a variety of techniques including laser Doppler flowmetry and hydrogen gas clearance (Dipette et al, 1987;Bauerfeund et al,1989;Li et al, 1991;. Intravenous infusion of a-CGRP can reverse the vasoconstrictor action of ET-1 on the internal carotid vascular bed in the rat (Gardiner et al, 1990), and local a-CGRP administration reduces the vasoconstriction induced by ET-1 in rabbit skin (Brain et al, 1988).…”

Differential effects of (±)‐dobutamine and human α‐CGRP on cardiac and on regional haemodynamics in conscious Long Evans rats

“…It is likely the latter was due to a venodilator action of human a-CGRP (Tornebrandt et al, 1987;Crossman et al, 1987; but see Al-Kazwini et al, 1987;Marshall et al, 1988). The present results, therefore, provide some explanation for the conflicting data in the literature regarding the cardiac haemodynamic effects of CGRP (DiPette et al, 1987;Lappe et al, 1987;Siren & Feuerstein, 1988;Ando et al, 1990) (see Introduction), since it is apparent that the effects of the peptide depend on the dose used. Moreover, it may be that the cardiac haemodynamic responses to bolus injections of CGRP would give a less clear picture of the interrelated changes that were seen in the present study, particularly with the infusion of the higher dose of human a-CGRP.…”

“…However, results of experiments in rats are less clearcut, possibly because of limitations with the methodology used. Thus, there have been two studies (DiPette et al, 1987;Ando et al, 1990) using the radiolabelled microsphere technique in acutely prepared rats (3 h post surgery), in which single measurements of cardiac output were made at a fixed time point after bolus injections of CGRP. Using this approach DiPette et al (1987) observed a small increase, while Ando et al (1990) found no change, in cardiac output after administration of rat and human a-CGRP, respectively.…”

Calcitonin gene-related peptide gene expression in the spontaneously hypertensive rat.

“…6 ' 7 The mechanism of blood pressure reduction is by peripheral arterial dilation, which reduces total peripheral resistance. 7 In addition to its vasodilator properties, CGRP has marked positive chronotropic and inotropic effects. 8 Immunocytochemical techniques have identified CGRP-containing nerve fibers throughout the cardiovascular system, particularly in association with blood vessels 9 ; the coronary circulation appears to be especially sensitive to the vasodilator effects of CGRP.…”