THROMBOXANE A(2)-PROSTAGLANDIN H-2 AND RENOVASCULAR HYPERTENSION IN RATS

To evaluate the contribution of thromboxane (Tx) Az-prostaglandin (PG) H-2 in two-kidney, one-clip Goldblatt hypertension (GH), 26 GH rats were chronically treated (GHT) with a specific TxA(2)-PGH(2) receptor antagonist, CGS-22652 (30 mg.kg(-1).24 h(-1) sc); 28 others as well as 17 sham-clipped (SC) rats received vehicle. Twelve GH and 3 GHT rats developed malignant hypertension and died. After 6 wk of treatment, GH rats exhibited higher mean blood pressure (BP; 189 +/- 3 vs. 118 +/- 2 mmHg) and an increased vascular reactivity to the main presser agents compared with SC rats. Chronic TxA(2)-PGH(2) receptor blockade lowered mean BP in 13 GHT rats (125 +/- 3 mmHg) and decreased their vascular reactivity compared with GH rats. However, 10 GHT rats remained hypertensive (190 +/- 9 mmHg) and differed from the former by an increased vascular reactivity to vasopressin. It is concluded that renal artery clipping induces either benign or malignant hypertension. In benign forms, TxA(2)-PGH(2) blockade normalizes BP through decreasing the vascular responsiveness to the main presser agents. In malignant forms, it limits the elevation of BP and markedly reduces mortality.