Effects of enalapril and L-158809 on myocardial beta-adrenergic receptor density in transplanted rat hearts.

BACKGROUND: We compare the effects of angiotensin-converting enzyme (ACE) inhibitor or angiotensin II type 1 (AT(1)) receptor blocker on density of myocardial beta-adrenergic receptors (beta-ARs) in a heterotopic heart transplantation model. METHODS: Hearts of F344 rats were heterotopically transplanted into Lewis rat recipients immunosuppressed with cyclosporine (10 mg/kg/day). Recipients were treated orally with the AT(1) receptor blocker L-158809 (3 mg/kg/day, n = 6), enalapril (3 mg/kg/day, n = 6), or vehicle only (n = 6) for 90 days. Density of myocordial beta-ARs was determined with an autoradiographic technique using [(3)H]CGP-12177. RESULTS: Graft status, the sum of the functional score and the score for color, was preserved better in the L-158809-treated group (5.8 +/- 0.9) and in the enalapril-treated group (5.6 +/- 0.8) than in the vehicle-treated group (3.8 +/- 0.9, p < 0.05). The grades of graft coronary artery disease in the L-158809-treated group and in the enalapril-treated group were significantly less than that seen in the vehicle-treated group. The density of myocardial beta-AR (fmol/mg of protein) was 3.5 +/- 0.5 in the L-158809-treated group (p < 0.05 vs. vehicle-treated group) and 3.2 +/- 0.5 (p < 0.05) in the enalapril-treated group but was 2.2 +/- 0.4 in the vehicle-treated group. CONCLUSION: L-158809 is as effective as enalapril in restoring myocardial beta-AR density in immunosuppressed rat transplant model, and this efficacy, as well as the prevention of graft coronary arteriosclerosis, is probably associated with the preservation of graft status.