REGRESSION OF HYPERTROPHY AFTER MYOCARDIAL-INFARCTION IS PRODUCED BY THE CHRONIC BLOCKADE OF ANGIOTENSIN TYPE-1 RECEPTOR IN RATS

The efficacy of angiotensin converting enzyme (ACE) inhibitors is well known to prevent the formation of angiotensin II (Ang II) by these ag ents. The objective of the present study was to evaluate the hemodynam ic, biochemical, and morphological responses to Ang II receptor blocka de with E-4177, arboxybiphenyl-4-yl)methyl]-2-cyclopropyl-7-methyl 3H- imidazol[4,5-b] pyridine, in rats with a healing myocardial infarction that had been induced by the surgical occlusion of the left main coro nary artery, The left ventricular weight increased 8 and 12 weeks afte r Infarction in comparison to that in sham-operated rats. Among the ra ts with experimental infarction, treatment with E-4177 significantly d ecreased the left ventricular weight. Although the infarct size was no t affected by E-4177, its administration ameliorated the elevated end- diastolic pressure and reduced the systolic pressure. The effects of t his agent on the levels of Ang II type 1 (AT1) receptor mRNA and ACE m RNA were evaluated in the non-infarcted myocardium by reverse transcri ptase polymerase chain reaction and binding assays, Treatment with E-4 177 reduced both the elevated AT1 mRNA and the number of Ang II recept ors, but not the ACE mRNA or ACE activity. While the receptor affinity remained unchanged with this agent, the collagen concentration was de creased. On the other hand, the depressed Na+/Ca2+ exchange activity w as restored in the non-infarcted myocardium at 8 and 12 weeks after in jury to the level seen in the sham-operated rats. These findings sugge st that the AT1 receptor antagonist, E-4177, has a beneficial effect o n the hemodynamics in spite of the lack of any improvement in the infa rct size. These observations may be partly attributed to the preventio n of angiotensin II formation during the period of post-infarction hea ling. (C) 1996 Academic Press Limited