Differential effects of Angiotensin AT1 and AT2 receptors on the expression, translation and function of the Na+-H+ exchanger and Na+-HCO3- symporter in the rat heart after myocardial infarction

• Published in: Journal of the American College of Cardiology 2001-06, Vol.37 (8), p.2154-2165
• Main Authors: SANDMANN, Steffen, MINGHUAN YU, KASCHINA, Elena, BLUME, Annegret, BOUZINOVA, Elena, AALKJAER, Christian, UNGER, Thomas
• Format: Article
• Language: English
• Subjects: Angiotensin I; Angiotensin II; Animals; Bicarbonates - metabolism; Biological and medical sciences; Blotting, Northern; Cardiology. Vascular system; Carrier Proteins - metabolism; Coronary heart disease; Heart; Male; Medical sciences; Myocardial Infarction - metabolism; Myocardium - metabolism; Random Allocation; Rats; Rats, Wistar; Receptors, Angiotensin - physiology; Renin-Angiotensin System - physiology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Sodium-Bicarbonate Symporters; Sodium-Hydrogen Exchangers - metabolism
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/S0735-1097(01)01287-6

This study investigated the role of angiotensin receptor subtype 1 (AT1) and angiotensin receptor subtype 2 (AT2) in the regulation of Na+-H+ exchanger (NHE) and Na+-HCO3 symporter (NBC) in the infarcted myocardium. The cardiac renin-angiotensin system is activated after myocardial infarction (MI), and both angiotensin AT1 and AT2 receptors are upregulated in the myocardium. Na+-H+ exchanger isoform-1 and NBC-1 gene expression were determined by reverse transcription polymerase chain reaction and Northern blot analysis; protein levels by Western blot analysis; and activity by measurement of H+ transport in left ventricular (LV) free wall, interventricular septum (IS) and right ventricle (RV) after induction of MI. Rats were treated with placebo, the angiotensin-converting enzyme inhibitor ramipril (1 mg/kg/day), the AT1 receptor antagonist valsartan (10 mg/kg/day) or the AT2 receptor antagonist PD 123319 (30 mg/kg/day). Treatment was started seven days before surgery. Na+-H+ exchanger isoform-1 and NBC-1 messenger RNA (mRNA) expression and protein levels were increased twofold in the LV free wall after MI, whereas no changes were observed in the IS and RV. Na+-dependent H+ flux was increased in the LV free wall. Ramipril inhibited mRNA and protein upregulation of both transporters. Valsartan inhibited the upregulation of NHE-1 mRNA and protein but had no effect on NBC-1 mRNA expression and translation. In contrast, PD 123319 abolished the upregulation of NBC-1 mRNA and protein but had no effect on NHE-1 upregulation. Ramipril and valsartan prevented post-MI increase in NHE-1 activity, whereas ramipril and PD 123319 decreased NBC-1 activity. Angiotensin II via its AT1 and AT2 receptors differentially controls transcriptional and translational regulation as well as the activity of NHE-1 and NBC-1 in the ischemic myocardium and contributes to the control of pH regulation in cardiac tissue.