Cardiovascular effects of central calcitonin gene-related peptide in conscious rats.
Calcitonin gene-related peptide (CGRP) is a potent peripheral vasodilator. In the present study, the cardiovascular effects of centrally administered CGRP were examined in conscious, normotensive rats. The rats were chronically instrumented with miniaturized pulsed Doppler flow probes to allow measurement of regional blood flow in the conscious animals. Injection of increasing doses of CGRP (0.3 to 3.0 micrograms/kg) in the lateral cerebroventricles transiently increased arterial pressure (maximal change = 13 +/- 3 mm Hg) and markedly increased heart rate (maximal increase = 88 +/- 10 b/min). The heart rate response was sustained over a period of 20 to 30 minutes. Central CGRP decreased hindquarter vascular resistance but had no effect on renal or mesenteric vascular resistances. In contrast, intravenous injections of CGRP reduced arterial pressure and renal, mesenteric, and hindquarter vascular resistances. The tachycardia response to central CGRP was attenuated by pretreatment with propranolol or hexamethonium, indicating that the heart rate response was mediated, in part, through increases in cardiac sympathetic tone. These data indicate that central CGRP may alter cardiovascular function through alterations in sympathetic outflow.
Lappe
R W
RW
Division of Experimental Therapeutics, Wyeth Laboratories, Inc., Philadelphia, PA 19101.
Todt
J A
JA
Wendt
R L
RL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002116:Calcitonin / Q000008:administration & dosage / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide; D003243:Consciousness; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D009479:Neuropeptides; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide