Author + information
- Received November 17, 2000
- Revision received February 16, 2001
- Accepted March 1, 2001
- Published online June 15, 2001.
- Steffen Sandmann, PhD∗,
- Minghuan Yu, MD∗,
- Elena Kaschina, MD∗,
- Annegret Blume, PhD∗,
- Elena Bouzinova, PhD†,
- Christian Aalkjaer, MD† and
- Thomas Unger, MD∗,* ()
- ↵*Reprint requests and correspondence:
Dr. Thomas Unger, Institute of Pharmacology, University of Kiel, Hospitalstr. 4, 24105 Kiel, Germany
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 AT1and AT2receptors 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 AT1receptor antagonist valsartan (10 mg/kg/day) or the AT2receptor 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 AT1and AT2receptors 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.
☆ Supported by grants from the Sonderforschungsbereich (SFB) 415 of the Deutsche Forschungsgemeinschaft (DFG), the German Institute for High Blood Pressure Research (Heidelberg, Germany) and the Danish Research Council (Aarhus, Denmark).
- Received November 17, 2000.
- Revision received February 16, 2001.
- Accepted March 1, 2001.
- American College of Cardiology