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  • Title: 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.
    Author: Sandmann S, Yu M, Kaschina E, Blume A, Bouzinova E, Aalkjaer C, Unger T.
    Journal: J Am Coll Cardiol; 2001 Jun 15; 37(8):2154-65. PubMed ID: 11419902.
    Abstract:
    OBJECTIVES: 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. BACKGROUND: The cardiac renin-angiotensin system is activated after myocardial infarction (MI), and both angiotensin AT1 and AT2 receptors are upregulated in the myocardium. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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