Effect of Indomethacin on Blood Pressure in the Normotensive Unanaesthetized Rabbit: Possible Relation to Prostaglandin Synthesis Inhibition

Abstract

1. To test the hypothesis that endogenous prostaglandins contribute to the regulation of blood pressure, we studied the effect of an inhibitor of prostaglandin synthesis, indomethacin, on mean aortic blood pressure in the normotensive, unanaesthetized rabbit. 2. Daily administration of indomethacin at 42 mumol/kg subcutaneously, but not of vehicle only, for 14 consecutive days, elevated the average mean arterial pressure in seven rabbits from 88 +/- 3 mmHg on the last day of the control period to 105 +/- 3 mmHg (P less than 0.01) and 107 +/- 2 mmHg (P less than 0.01) on days 6 and 14 of indomethacin treatment respectively, and reduced the urinary excretion of prostaglandin-like substance from 1.06 +/- 0.26 to 0.17 +/- 0.05 nmol of prostaglandin E2 equivalents/day (P less than 0.05; n = 5). Neither indomethacin nor the vehicle affected the intake of water, the 24 h urine volume, the cumulative difference between sodium intake and urinary sodium excretion, or the plasma volume. 3. The results of the study are compatible with the hypothesis that one or more prostaglandins contribute to maintain normotension in the rabbit and that reduction in prostaglandin biosynthesis may cuase blood pressure to rise.