This Article Full Text Full Text (PDF) All Versions of this Article: 40/1/107    most recent 01.HYP.0000023226.50264.42v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mori, Y. Articles by Matsuoka, H. Search for Related Content PubMed PubMed Citation Articles by Mori, Y. Articles by Matsuoka, H. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Related Collections Hypertension - basic studies

(Hypertension. 2002;40:107.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Long-Term Adrenomedullin Infusion Improves Survival in Malignant Hypertensive Rats

Yosuke Mori; Toshio Nishikimi; Naohiko Kobayashi; Hidehiko Ono; Kenji Kangawa; Hiroaki Matsuoka

From the Department of Hypertension and Cardiorenal Medicine, Dokkyo University School of Medicine (Y.M., T.N., N.K., H.O., H.M.), Mibu, Tochigi; and the Research Institute National Cardiovascular Center (K.K.), Suita, Osaka, Japan.

Correspondence to Toshio Nishikimi, MD, Department of Hypertension and Cardiorenal Medicine, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan. E-mail nishikim{at}dokkyomed.ac.jp

Previous studies have demonstrated that adrenomedullin has inhibitory effects on the proliferation and DNA synthesis of mesangial cells and vascular smooth muscle cells in vitro and that plasma adrenomedullin levels are markedly elevated in malignant hypertension. This study was designed to examine whether chronic adrenomedullin infusion has renoprotective effects in malignant hypertensive rats. We studied the following 3 groups: control Wistar Kyoto rats, deoxycorticosterone acetate–salt spontaneously hypertensive rats, and adrenomedullin-treated deoxycorticosterone acetate–salt spontaneously hypertensive rats. Chronic adrenomedullin infusion using an osmotic minipump was started simultaneously with deoxycorticosterone acetate–salt treatment. After 3 weeks of the treatment, malignant hypertensive rats were characterized by higher blood pressure, kidney weight, urinary protein excretion, glomerular injury score, plasma renin concentration, aldosterone level, endogenous rat plasma adrenomedullin level, renal cortical tissue angiotensin II level, angiotensin-converting enzyme mRNA level, and transforming growth factor-ß1 mRNA level in the renal cortex, and by lower creatinine clearance, compared with the control rats. Chronic adrenomedullin infusion significantly improved these parameters (kidney weight -6.5%, urinary protein excretion -63.8%, glomerular injury score -38.3%, plasma renin concentration -52.4%, aldosterone -23.2%, rat adrenomedullin -28.6%, renal angiotensin II -28.1%, renal angiotensin-converting enzyme mRNA -38.3%, renal transforming growth factor-ß1 mRNA -56.2%, and creatinine clearance +20.5%) without significant reduction of mean arterial pressure (-4%). Kaplan-Meier survival analysis showed that adrenomedullin infusion significantly prolonged survival time. These results suggest that subdepressor dose of chronic adrenomedullin infusion has renoprotective effects in this malignant hypertension model, at least in part, via inhibition of the circulating and intrarenal renin-angiotensin system.

Key Words: adrenomedullin • hypertension, malignant • renal disease • renin-angiotensin system • renal circulation

This article has been cited by other articles:

				M. Rahman, A. Nishiyama, P. Guo, Y. Nagai, G.-X. Zhang, Y. Fujisawa, Y.-Y. Fan, S. Kimura, N. Hosomi, K. Omori, et al. Effects of Adrenomedullin on Cardiac Oxidative Stress and Collagen Accumulation in Aldosterone-Dependent Malignant Hypertensive Rats J. Pharmacol. Exp. Ther., September 1, 2006; 318(3): 1323 - 1329. [Abstract] [Full Text] [PDF]

				Y. Ishikawa, T. Nishikimi, K. Akimoto, K. Ishimura, H. Ono, and H. Matsuoka Long-Term Administration of Rho-Kinase Inhibitor Ameliorates Renal Damage in Malignant Hypertensive Rats Hypertension, June 1, 2006; 47(6): 1075 - 1083. [Abstract] [Full Text] [PDF]

				S. Fukuhara, A. Sakurai, H. Sano, A. Yamagishi, S. Somekawa, N. Takakura, Y. Saito, K. Kangawa, and N. Mochizuki Cyclic AMP Potentiates Vascular Endothelial Cadherin-Mediated Cell-Cell Contact To Enhance Endothelial Barrier Function through an Epac-Rap1 Signaling Pathway Mol. Cell. Biol., January 1, 2005; 25(1): 136 - 146. [Abstract] [Full Text] [PDF]

				M. Luodonpaa, H. Leskinen, M. Ilves, O. Vuolteenaho, and H. Ruskoaho Adrenomedullin modulates hemodynamic and cardiac effects of angiotensin II in conscious rats Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2004; 286(6): R1085 - R1092. [Abstract] [Full Text] [PDF]

				P. Sandner, K. H. Hofbauer, H. Tinel, A. Kurtz, H. C. Thiesson, P. D. Ottosen, S. Walter, O. Skott, and B. L. Jensen Expression of adrenomedullin in hypoxic and ischemic rat kidneys and human kidneys with arterial stenosis Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2004; 286(5): R942 - R951. [Abstract] [Full Text] [PDF]

				T. Nishikimi, F. Yoshihara, S. Horinaka, N. Kobayashi, Y. Mori, K. Tadokoro, K. Akimoto, N. Minamino, K. Kangawa, and H. Matsuoka Chronic Administration of Adrenomedullin Attenuates Transition From Left Ventricular Hypertrophy to Heart Failure in Rats Hypertension, November 1, 2003; 42(5): 1034 - 1041. [Abstract] [Full Text] [PDF]

				I. M.C. Dixon A new altruist on the block: effects of adrenomedullin after myocardial infarction Cardiovasc Res, December 1, 2002; 56(3): 347 - 349. [Full Text] [PDF]