Endogenous calcitonin gene-related peptide modulates tachycardiac but not bradycardiac baroreflex in rats.
Effects of intracisternally administered human calcitonin gene-related peptide (8-37) [hCGRP-(8-37)], an antagonist, and hCGRP, an agonist of the CGRP receptor in the rat central nervous system, on baroreflex sensitivity (BRS) were studied in conscious male rats. Each rat sequentially received intracisternally injected 0.9% saline and then hCGRP-(8-37) at doses of 1, 2.5, and 5 nmol in a volume of 10 microliters at an interval of 15 min. Five minutes after each injection, sodium nitroprusside (SNP, 10 micrograms/kg) or phenylephrine hydrochloride (PE, 2 micrograms/kg) was intravenously administered to induce reflex tachycardia or bradycardia, respectively. Intracisternally administered hCGRP-(8-37) increased BRS of the reflex tachycardia induced by SNP in a dose-related manner but did not change the BRS after PE. Intracisternally injected hCGRP significantly decreased the BRS after SNP. The lowering effect of hCGRP on BRS after SNP was inhibited by hCGRP-(8-37) injected before hCGRP. These results suggest that endogenous CGRP in the lower brain stem is selectively involved in the tachycardiac but not the bradycardiac baroreflex and modulates the baroreflex in an inhibitory rather than facilitatory fashion.
Kim
S
S
Department of Physiology, Jichi Medical School, Tochigi, Japan.
Ouchi
Y
Y
Sekiguchi
H
H
Fujikawa
H
H
Shimada
K
K
Yagi
K
K
D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008916:Miotics / Q000008:administration & dosage*; D010446:Peptide Fragments / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000819:agonists / Q000502:physiology*
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D008916:Miotics; D010446:Peptide Fragments; D018015:Receptors, Calcitonin Gene-Related Peptide; C058636:calcitonin gene-related peptide (8-37); D015740:Calcitonin Gene-Related Peptide