Angiotensin II receptor blockade after myocardial infarction in rats: effects on hemodynamics, myocardial DNA synthesis, and interstitial collagen content.
Angiotensin-converting enzyme (ACE) inhibitors are widely used for treatment of heart failure after myocardial infarction (MI). The beneficial effects consist of a combination of hemodynamic effects and interference with cardiac structural alterations. These effects are believed to depend on inhibition of angiotensin II (AII) formation and thus diminished angiotensin receptor stimulation. We administered the angiotensin II-1 (AT-1) receptor antagonist losartan during and after completion of the repair phase of an MI to investigate involvement of the AT-1 receptor in the above described effects of captopril. MI reduced cardiac output (CO) (sham 94 +/- 4 ml/min, MI 78 +/- 5 ml/min) and maximal CO (sham 154 +/- 4, MI 107 +/- 5 ml/min, respectively). Losartan (15 mg/kg/day) resulted in a rightward shift of the AII pressor dose-response curve by a factor of 32-40. Neither CO nor COVL,max was affected by losartan treatment in either phase (late treatment CO = 78 +/- 5, COVL,max = 118 +/- 9 ml/min). Although early treatment with losartan reduced cardiac hypertrophy measured as heart weight, DNA synthesis was reduced only slightly. In contrast, collagen deposition was inhibited completely. The results suggest that the effects of captopril in rats after MI are not dependent on AT-1 receptor-mediated mechanisms.
D000804:Angiotensin II / Q000037:antagonists & inhibitors; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003094:Collagen / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D019808:Losartan; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D003094:Collagen; D004247:DNA; D019808:Losartan