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

Abstract

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 × 20 min control clearances collected. Endothelin-1 (100 ηg 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<0.01) with endothelin alone, from 103 ± 6 to 135 ± 6 mmHg (p<0.01) with endothelin plus meclofenamate, and from 105 ± 6 to 131 ± 10 mmHg (p<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<0.01) with endothelin alone, from 2.3 ± 0.5 to 0.7 ± 0.4 ml/min (p<0.01) with endothelin plus meclofenamate, and from 2.6 ± 0.4 to 0.6 ± 0.4 ml/min (p<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.