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 sodium-handling effects of angiotensin-converting enzyme (ACE) inhibition after myocardial infarction (MI). We studied rats after coronary artery ligation treated for 3 weeks with captopril or losartan (2 g/L drinking water for each agent). Hemodynamic and renal function studies were performed in conscious rats before and after sequential infusion BK inhibitor (BKI, 0.02 ng/kg/min) and indomethacin (1 mg/kg). Myocardial infarction increased filtration fraction (FF) 20% (p < .004) but did not change glomerular filtration rate (GFR), urine flow (UF), renal blood flow (RBF), renal vascular resistance (RVR), urine sodium (UNa), or fractional excretion of sodium (FENa). Captopril decreased (p < 0.001) mean arterial pressure (MAP) 25%, UF 61%, RVR 65%, and FENa 75% and 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 rats, 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 losartan-treated MI rats, BKI increased (p < 0.05) UNa 42% and FENa 60%, whereas indomethacin increased (p < 0.05) UNa 79% and FENa 85%. Activation of the BK and prostaglandin systems may play an important role in regulating renal function during chronic ACE inhibition, primarily by enhancing the renal vasodilatory effects of angiotensin II (AII) blockade.
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Department of Internal Medicine, Department of Veterans Affairs Medical Center, Tucson, Arizona, USA.
Gaballa
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Raya
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D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001713:Biphenyl Compounds / Q000627:therapeutic use; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D002216:Captopril / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000627:therapeutic use; D007213:Indomethacin / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007677:Kidney Function Tests; D019808:Losartan; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D065168:Bradykinin Receptor Antagonists; D016861:Cyclooxygenase Inhibitors; D007093:Imidazoles; D013777:Tetrazoles; D002216:Captopril; C053010:NPC 567; D019808:Losartan; D001920:Bradykinin; D007213:Indomethacin