This Article Full Text Full Text (PDF) All Versions of this Article: 41/3/493    most recent 01.HYP.0000056769.73726.E5v1 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 Fujisawa, G. Articles by Ishibashi, S. Search for Related Content PubMed PubMed Citation Articles by Fujisawa, G. Articles by Ishibashi, S. Related Collections Hypertension - basic studies

(Hypertension. 2003;41:493.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Na/H Exchange Isoform 1 Is Involved in Mineralocorticoid/Salt-Induced Cardiac Injury

Genro Fujisawa; Koji Okada; Shigeaki Muto; Nobuya Fujita; Naoki Itabashi; Eiji Kusano; Shun Ishibashi

From the Divisions of Endocrinology and Metabolism and Nephrology, Department of Internal Medicine, Jichi Medical School, Minamikawachi, Tochigi, Japan.

Correspondence to Genro Fujisawa, MD, Division of Endocrinology and Metabolism, Jichi Medical School, Minamikawachi, Tochigi, 329-0498 Japan. E-mail genrfjs{at}attglobal.net

Long-term exposure of uninephrectomized rats to desoxycorticosterone acetate (DOCA)/salt induces cardiac fibrosis and hypertrophy through mineralocorticoid receptors (MRs). However, the underlying cellular mechanisms remain unclear. To determine whether Na/H exchange isoform 1 (NHE1) is involved in the cellular mechanisms, we examined the effects of a specific NHE1 inhibitor, cariporide, and an MR antagonist, spironolactone, on DOCA/salt-induced cardiac fibrosis and hypertrophy. Uninephrectomized rats were given 20 mg of DOCA (single subcutaneous injection) plus 0.9% NaCl/0.3% KCl to drink and were killed at 8 days. Two groups of rats given DOCA/salt were treated with either spironolactone (50 mg/kg per day SC) or cariporide (30 mg/kg per day PO) for 8 days. Control rats were treated with only high salt after the operation. The DOCA/salt-induced perivascular collagen deposition was completely abolished by cariporide and spironolactone. DOCA/salt-induced interstitial collagen deposition was partially and completely suppressed by spironolactone and cariporide, respectively. The rats exposed to DOCA/salt had cardiocyte hypertrophy in the subendocardial and subepicardial regions, a finding that was completely inhibited by cariporide but not by spironolactone. In rats given DOCA/salt, NHE1 protein expression was markedly increased. This was partially and completely reversed by spironolactone and cariporide, respectively. We concluded that cardiac NHE1 contributes to DOCA/salt-induced cardiac fibrosis and hypertrophy and that the NHE1 inhibitor cariporide completely prevents the detrimental effects of DOCA/salt on the heart. We also demonstrated that DOCA/salt-induced cardiac injury through the MRs partly occurs through NHE1 activation.

Key Words: mineralocorticoids • fibrosis • hypertrophy • collagen • sodium-hydrogen exchanger

This article has been cited by other articles:

				Y. Iwazu, S. Muto, G. Fujisawa, E. Nakazawa, K. Okada, S. Ishibashi, and E. Kusano Spironolactone Suppresses Peritubular Capillary Loss and Prevents Deoxycorticosterone Acetate/Salt-Induced Tubulointerstitial Fibrosis Hypertension, March 1, 2008; 51(3): 749 - 754. [Abstract] [Full Text] [PDF]

				H. E. Cingolani and I. L. Ennis Sodium-Hydrogen Exchanger, Cardiac Overload, and Myocardial Hypertrophy Circulation, March 6, 2007; 115(9): 1090 - 1100. [Full Text] [PDF]

				D. W. Jones Dietary Sodium and Blood Pressure Hypertension, May 1, 2004; 43(5): 932 - 935. [Full Text] [PDF]

				M. Karmazyn, Q. Liu, X. T. Gan, B. J. Brix, and L. Fliegel Aldosterone Increases NHE-1 Expression and Induces NHE-1-Dependent Hypertrophy in Neonatal Rat Ventricular Myocytes Hypertension, December 1, 2003; 42(6): 1171 - 1176. [Abstract] [Full Text] [PDF]