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.
OBJECTIVE
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.
Sandmann
S
S
Institute of Pharmacology, University of Kiel, Germany.
Yu
M
M
Kaschina
E
E
Blume
A
A
Bouzinova
E
E
Aalkjaer
C
C
Unger
T
T
D000803:Angiotensin I; D000804:Angiotensin II; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000378:metabolism*; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027982:Sodium-Bicarbonate Symporters; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*
D001639:Bicarbonates; D002352:Carrier Proteins; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D027982:Sodium-Bicarbonate Symporters; D017923:Sodium-Hydrogen Exchangers; D000804:Angiotensin II; D000803:Angiotensin I