Cardiorenal actions of endothelin, Part II: Effects of cyclooxygenase inhibitors

The effects of cyclooxygenase inhibitors (meclofenamate and indomethacin) on endothelin-induced changes in renal function were evaluated in pentobarbital anesthetized female rats. Two groups (n = 5/group) of rats were evaluated: one group received a continuous intravenous infusion of meclofenamate (0.03 mg kg-1 min-1) and the second group received a bolus injection of indomethacin (5 mg/kg). Following surgery, rats were allowed 60 min to stabilize and 3 X 20 min control clearances collected. Endothelin-1 (100 eta kg-1 min-1) was then added into the infusate for 30 min. Neither meclofenamate nor indomethacin caused significant changes on endothelin-induced systemic vasoconstriction; blood pressure increased from 107 +/- 3 to 136 +/- 2 mmHg (p less than 0.01) with endothelin alone, from 103 +/- 6 to 135 +/- 6 mmHg (p less than 0.01) with endothelin plus meclofenamate, and from 105 +/- 6 to 131 +/- 10 mmHg (p less than 0.01) with endothelin plus indomethacin. Similarly, endothelin-induced decreases in glomerular filtration rate (GFR) were not affected by either meclofenamate or indomethacin; GFR decreased from 2.7 +/- 0.2 to 0.8 +/- 0.3 ml/min (p less than 0.01) with endothelin alone, from 2.3 +/- 0.5 to 0.7 +/- 0.4 ml/min (p less than 0.01) with endothelin plus meclofenamate, and from 2.6 +/- 0.4 to 0.6 +/- 0.4 ml/min (p less than 0.01) with endothelin plus indomethacin. Baseline excretion rates of sodium, potassium and urine volume were also not affected by the inhibitors of cyclooxygenase. These data demonstrate that, under the conditions of the current study, endothelin-induced changes in renal and cardiovascular function are not affected by inhibiting prostaglandin production.