Renal hemodynamics and blood flow autoregulation during acute cyclooxygenase inhibition in male rats

Abstract

After the acute inhibition of prostanoid synthesis, adjustments of renal hemodynamics may not be characterized immediately. Therefore, time-related effects of indomethacin on hemodynamics and renal blood flow (RBF) autoregulation were studied in anesthetized euvolemic male rats injected intravenously with vehicle, indomethacin (3, 4, or 5 mg/kg body wt), or meclofenamate (4 or 5 mg/kg body wt). Hemodynamics and RBF autoregulation were not influenced by vehicle injection, nor by time (n = 6). In contrast, mean arterial pressure (MAP) decreased significantly from 117 +/- 4 to 103 +/- 3 mmHg, and RBF progressively and significantly increased from 8.00 +/- 0.34 to 9.17 +/- 0.50 ml/min in the 3 mg/kg body wt indomethacin group (n = 8). Treatment with the higher doses of indomethacin (n = 9) or meclofenamate (n = 6) did not change RBF, while MAP decreased by 15 mmHg. A time-dependent significant enhancement of RBF autoregulatory efficiency was found in the drug-treated rats. Changes in renal function and reductions of prostanoid excretion in urine, of plasma renin activity, or serum aldosterone were similar in the nonsteroidal antiinflammatory drug groups. In conclusion, our findings demonstrate important time-related adjustments of renal hemodynamics in male rats treated with indomethacin, especially with the lower dose (3 mg/kg body wt iv). The factor(s) responsible for the hemodynamic changes remains unknown.