Effects of differential blockade of the renin-angiotensin system in postinfarcted rats.
The present study compared short-term effects of the AT(1)-receptor antagonist, irbesartan with the angiotensin-converting enzyme (ACE) inhibitor, enalapril on systemic haemodynamics and cardiac remodelling in post-myocardia-infarcted (MI) rats. MI Sprague-Dawley rats were orally treated for 4 weeks with irbesartan (50 mg/kg/day) or enalapril (10 mg/kg/day). Then, cardiac and systemic haemodynamics were measured. Compared with the sham-operated group, left ventricular end-diastolic pressure (LVEDP), diastolic pressure (LVDP), heart weight to body weight ratio were all significantly increased in the MI group while the LV contractility (dP/dt) and pulsatile arterial pressure were significantly reduced. Both drugs reduced the elevated LVEDP and LVDP and prevented cardiac hypertrophy. Furthermore, irbesartan attenuated the right shift of the pressure-volume curves, prevented postinfarction-induced increase in urinary cyclic guanosine monophosphate and reduced urinary aldosterone excretion. Although both drugs were able to prevent further cardiac hypertrophy and improved cardiac filling pressure, only irbesartan limited LV dilatation. These data indicate that blockade of the renin-angiotensin system at the level of AT1 receptors may have a better cardioprotective benefit than reducing angiotensin II levels by ACE inhibition.
Lacour
Colette
C
Cardiovascular Thrombosis Department, Sanofi-Synthélabo Recherche, 34184 Montpellier 04, France.
Roccon
Alain
A
Galindo
Gérard
G
Canals
Françoise
F
Hogie
Manuela
M
Segondy
Danielle
D
Briand
Danielle
D
Roque
Claude
C
Herbert
Jean-Marc
JM
Nisato
Dino
D
D000450:Aldosterone / Q000652:urine; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D006152:Cyclic GMP / Q000652:urine; D004656:Enalapril / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D000077405:Irbesartan; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology*; D020257:Ventricular Remodeling / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000450:Aldosterone; D004656:Enalapril; D006152:Cyclic GMP; D000077405:Irbesartan