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1 Research Equipment Center, Kagawa University, Kagawa, Japan
2 Department of Applied Pharmacology and Therapeutics, Osaka City University Medical School, Osaka, Japan
3 Department of Pharmacology, Kagawa University, Kagawa, Japan
* To whom correspondence should be addressed. E-mail: recfuji{at}kms.ac.jp.
Recently, a new member of the calcitonin gene-related peptide (CGRP) family was identified and named adrenomedullin2 (AM2) or intermedin (IMD). AM2/IMD has been shown to have a vasodilative effect in both mice and rats, and an effect on urine formation in rats. In the present study, we investigated the effects of intravenously infused rat AM2 (rAM2) on blood pressure (BP), heart rate (HR), renal sympathetic nerve activity (RSNA) and renal blood flow (RBF) in conscious unrestrained rats, relative to the effects of rat adrenomedullin (rAM) and proadrenomedullin N-terminal 20 peptide (rPAMP). Intravenous infusion of rAM2 (5 nmol/kg) significantly decreased BP and increased HR, RSNA and RBF. These hypotensive and sympathoexcitatory effects diminished after 20 min, and HR returned to control levels 30 min after cessation of the infusion. In contrast, a significant increase in RBF was still evident 60 min after cessation of the peptide infusion. The responses in BP, HR and RSNA were longer with rAM infusion (5 nmol/kg) than with rAM2 infusion, while the increase in RBF induced by rAM2 and rAM were similar in their amplitude and duration of activity. Infusion of rPAMP (200 nmol/kg) increased HR and RSNA, but had no effect on RBF. Baroreceptor-denervation suppressed the increases in HR and RSNA to rAM2, but did not diminish those responses. These findings indicate that the physiological roles of rAM2 are similar to rAM, and rAM2 also has a long-lasting vasodilative action on the renal vascular bed.
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