Indomethacin decreases arterial blood pressure and plasma renin activity in rats with aortic ligation.

Abstract

Severe renovascular hypertension was produced in rats by complete aortic ligation between the origin of the renal arteries. Six days after coarctation, a carotid cannula was implanted and mean arterial blood pressure (MABP) and plasma renin activity (PRA) were determined. Subsequently, indomethacin (5 mg/kg in oil) or vehicle was administered subcutaneously three times in the following 24-hour period. On day 7, MABP and PRA were again determined. Indomethacin reduced MABP from 179.0 +/- 6.7 to 156.5 +/- 8.8 mm Hg (P less than 0.002, n = 11) and PRA from 21.2 +/- 7.3 to 9.3 +/- 2.9 ng AI/ml per hr (P less than 0.045, n = 10), whereas vehicle treatment did not alter either MABP or PRA (n = 6). There was a significant association between the decrease in MABP and the percentage decrease in PRA following indomethacin treatment (r = 0.766, P less than 0.016). A similar study was performed in aortic ligated rats in which the left kidney was removed at the time of ligation. In these animals, 6 days after surgery, MABP and PRA were 128.0 +/- 5.9 mm Hg and 0.11 +/- 0.06 ng AI/ml per hr (n = 6), respectively, and indomethacin had no effect on either MABP or PRA. These data provide evidence that the prostaglandin system is involved in the release of renin and in the pathogenesis of elevated blood pressure in this model of renin-dependent hypertension.