title: Effects of differential blockade of the renin-angiotensin system in postinfarcted rats.
abstract: 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.
authors.affiliation: Cardiovascular Thrombosis Department, Sanofi-Synthélabo Recherche, 34184 Montpellier 04, France.
authors.forename: Colette
authors.initials: C
authors.lastname: Lacour
authors.forename: Alain
authors.initials: A
authors.lastname: Roccon
authors.forename: Gérard
authors.initials: G
authors.lastname: Galindo
authors.forename: Françoise
authors.initials: F
authors.lastname: Canals
authors.forename: Manuela
authors.initials: M
authors.lastname: Hogie
authors.forename: Danielle
authors.initials: D
authors.lastname: Segondy
authors.forename: Danielle
authors.initials: D
authors.lastname: Briand
authors.forename: Claude
authors.initials: C
authors.lastname: Roque
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Herbert
authors.forename: Dino
authors.initials: D
authors.lastname: Nisato
mesh_terms: 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
chemical_list: 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