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Am J Physiol Heart Circ Physiol 274: H1489-H1494, 1998;
0363-6135/98 $5.00
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Vol. 274, Issue 5, H1489-H1494, May 1998

Endogenous calcitonin gene-related peptide modulates tachycardiac but not bradycardiac baroreflex in rats

Seungbum Kim1,2, Yasuyoshi Ouchi2, Hiromichi Sekiguchi1, Hideyuki Fujikawa1, Kazuyuki Shimada1, and Kinji Yagi1

1 Departments of Physiology and Cardiology, Jichi Medical School, Minamikawachi, Tochigi 329-04; and 2 Department of Geriatrics, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113, Japan

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 µl at an interval of 15 min. Five minutes after each injection, sodium nitroprusside (SNP, 10 µg/kg) or phenylephrine hydrochloride (PE, 2 µg/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.

calcitonin gene-related peptide antagonist; intracisternal; baroreflex sensitivity; heart rate


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