Cardiovascular effects of rat calcitonin gene-related peptide in the conscious rat.
The role of rat calcitonin gene-related peptide (CGRP), a recently characterized vasoactive neuropeptide, in cardiovascular regulation was studied in the conscious rat. Mean arterial pressure (MAP), heart rate, cardiac output (thermodilution technique) and regional blood flow (directional pulsed Doppler velocimetry) were monitored after i.v. or i.c.v. administration of CGRP. Systemic administration of CGRP (0.1-10 nmol/kg i.v.) decreased MAP and increased heart rate in a dose-related manner. Cardiac output increased (+95 +/- 16 ml/min/kg, P less than .01) after the 1-nmol/kg dose. At the lower or higher doses, CGRP produced no consistent changes in cardiac output. Total peripheral resistance was decreased significantly at the doses of 1 and 10 nmol/kg of CGRP. The CGRP i.v. doses of 1 and 10 nmol/kg increased mesenteric and hindquarter blood flow to a maximum of +23 +/- 7 and +30 +/- 6%, respectively (P less than .01). An increase in renal blood flow (+19 +/- 6%, P less than .05) and a decrease in renal resistance (-15 +/- 4%, P less than .05) were produced by the 0.1-nmol/kg dose of CGRP which had no effect on MAP; higher doses of CGRP tended to decrease renal blood flow. The resistance in all vascular beds was decreased by the CGRP doses of 1 and 10 nmol/kg. The maximum decreases in mesenteric, renal and hindquarter vascular resistance after the 10-nmol/kg dose were -53 +/- 3, -42 +/- 5 and -48 +/- 4%, respectively (P less than .01). The hypotensive and vasodilator responses to CGRP i.v. were significantly magnified, and the tachycardia produced by CGRP was attenuated in the sinoaortic denervated rats. Atropine (muscarinic blockers), propranolol (beta adrenoceptor blocker), cimetidine and pyrilamine (histamine H1 and H2 blockers), indomethacin (prostaglandin synthesis inhibitor), BN52021 (platelet activating factor antagonist) or a substance P antagonist had no effect on the cardiovascular responses elicited by systemic CGRP. CGRP, i.c.v. (0.1-10 nmol/kg), induced a modest tachycardia in both intact and sinoaortic denervated rats, but was devoid of any other cardiovascular effects. The results indicate that CGRP is a potent vasodilator of mesenteric, renal and hindquarter skeletal muscle blood vessels in the conscious rat. The hypotensive and vasodilator actions of circulating CGRP are likely to be mediated by direct peripheral interaction with CGRP receptors on vascular smooth muscle, whereas its tachycardic effect seems to involve reflex activation of the sympathetic nervous system.
Sirén
A L
AL
Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
Feuerstein
G
G
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide; D003714:Denervation; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D013373:Substance P / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects
D009479:Neuropeptides; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide