RELATIVE CONTRIBUTION OF ANGIOTENSIN-II, BRADYKININ, AND PROSTAGLANDINS TO THE RENAL EFFECTS OF CONVERTING-ENZYME INHIBITION IN RATS AFTER CHRONIC MYOCARDIAL-INFARCTION

We wished to determine whether enhanced bioavailability of bradykinin (BK) and vasodilatory prostaglandins contribute to renovascular and so dium-handling effects of angiotensin-converting enzyme (ACE) inhibitio n after myocardial infarction (MI). We studied rats after coronary art ery ligation treated for 3 weeks with captopril or losartan (2 g/L dri nking water for each agent). Hemodynamic and renal function studies we re performed in conscious rats before and after sequential infusion BK inhibitor (BKI, 0.02 ng/kg/min) and indomethacin (1 mg/kg). Myocardia l infarction increased filtration fraction (FF) 20% (p < .004) but did not change glomerular filtration rate (GFR), urine flow (UF), renal b lood flow (RBF), renal vascular resistance (RVR), urine sodium (UNa), or fractional excretion of sodium (FENa). Captopril decreased (p < 0.0 01) mean arterial pressure (MAP) 25%, UF 61%, RVR 65%, and FENa 75% an d increased (p < 0.05) GFR 22%, and RBF 34%. Losartan decreased (p < 0 .05) MAP 27%, UF 52%, RVR 21%, and FENa 44%, In captopril-treated MI r ats, BKI decreased (p < 0.05) GFR 22% and RBF 25% and increased (p < 0 .05) RVR 32%, UNa 43%, and FENa 28%, whereas indomethacin decreased (p < 0.05) GFR 24% and increased (p < 0.05) UNa 86% and FENa 112%. In lo sartan-treated MI rats, BKI increased (p < 0.05) UNa 42% and FENa 60%, whereas indomethacin increased (p < 0.05) UNa 79% and FENa 85%. Activ ation of the BK and prostaglandin systems may play an important role i n regulating renal function during chronic ACE inhibition, primarily b y enhancing the renal vasodilatory effects of angiotensin II (AII) blo ckade.