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Am J Physiol Regul Integr Comp Physiol 274: R979-R984, 1998;
0363-6119/98 $5.00
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Vol. 274, Issue 4, R979-R984, April 1998

Central actions of adrenomedullin on cardiovascular parameters and sympathetic outflow in conscious rats

Mitsuhiko Saita1,2, Ayumi Shimokawa1, Takato Kunitake1, Kazuo Kato1, Takamitsu Hanamori1, Kazuo Kitamura2, Tanenao Eto2, and Hiroshi Kannan1

1 Department of Physiology and 2 Department of Internal Medicine, Miyazaki Medical College, Miyazaki 889-1692, Japan

Adrenomedullin (ADM) is reported to be a peripherally acting hypotensive peptide, but its central actions are unclear. We investigated the effects of centrally administered ADM on blood pressure (BP), heart rate (HR), and renal sympathetic nerve activity (RSNA) in conscious rats and sinoaortic-denervated (SAD) rats. We also investigated the receptors interacting with ADM using two putative antagonists. Intracerebroventricular administration of ADM in doses of 0.1 and 0.5 nmol/kg caused tachycardia and early inhibition of RSNA. Central ADM (1.0 nmol/kg) induced hypertension, tachycardia, and a decrease followed by an increase in RSNA. In SAD rats, increases in BP, HR, and RSNA at the late phase were enhanced by central ADM (1.0 nmol/kg), whereas the early decrease in RSNA remained. Thus the inhibition of RSNA via central ADM may be unrelated to the arterial baroreceptor reflex. Pretreatment with antagonists human calcitonin gene-related peptide-(8---37) and human ADM-(22---52) significantly suppressed the central actions of ADM. The findings suggest that ADM is involved as a neuropeptide in the receptor-mediated central regulation of the cardiovascular system and RSNA.

renal sympathetic nerve activity; sinoaortic-denervated rats; receptor antagonists; neuropeptide


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