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(Hypertension. 2001;37:216.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Alterations of Intrarenal Adrenomedullin and Its Receptor System in Heart Failure Rats

Fumiki Yoshihara; Toshio Nishikimi; Ichiro Okano; Takeshi Horio; Chikao Yutani; Hisayuki Matsuo; Shuichi Takishita; Tohru Ohe; Kenji Kangawa

From the Research Institute (F.Y., I.O., H.M., K.K.), Division of Hypertension (T.H., S.T.), Division of Pathology (C.Y.), National Cardiovascular Center, Osaka, Japan; Department of Cardiovascular Medicine (T.N.), Dokkyo Medical School, Tochigi, Japan; and Department of Cardiovascular Medicine (T.O.), Okayama University Medical School, Okayama, Japan.

Correspondence to Fumiki Yoshihara, MD, National Cardiovascular Center Research Institute, Fujishirodai, Suita, Osaka 565-8565, Japan. E-mail fyoshi{at}ri.ncvc.go.jp

Calcitonin receptor–like receptor/receptor activity–modifying protein 2 (CRLR/RAMP2) and CRLR/RAMP3 complexes have been reported to be specific adrenomedullin (AM) receptors. In the present study, we evaluated the pathophysiological significance of renal AM and its receptor system in aortocaval shunt (ACS) rats. Renal AM levels were measured serially during 5 weeks after the operation. Renal gene expressions of AM, CRLR, RAMP2, and RAMP3 were measured at 2 weeks (decompensated phase) and 5 weeks (compensated phase) after the operation. Immunohistochemical localizations of renal AM were also evaluated. Furthermore, the relations between urinary sodium excretion (UNaV) and renal AM levels were evaluated. Renal AM levels were higher in ACS than in control animals only at 1, 2, and 3 weeks after the operation. At 2 weeks after the operation, renal AM mRNA expression was also higher in ACS than in control animals. CRLR, RAMP2, and RAMP3 mRNAs were expressed in the kidney, but there were no differences between the 2 groups. Immunohistochemistry revealed the positive AM immunostaining within the renal tubular cells, and it was more intense in ACS than in control animals. There were significant correlations between UNaV and renal AM levels. At 5 weeks after the operation, there were no differences in mRNA levels of AM, CRLR, RAMP2, and RAMP3 between the 2 groups. There was a significant correlation between UNaV and medullary AM levels. The present findings suggest that increased renal AM levels in decompensated heart failure, presumably due to increased AM production in renal tubules, in part, are involved in the regulation of sodium excretion.

Key Words: adrenomedullin • receptors, adrenomedullin • kidney • heart failure • sodium

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