To evaluate the contribution of thromboxane (Tx) A2-prostaglandin (PG) H2 in two-kidney, one-clip Goldblatt hypertension (GH), 26 GH rats were chronically treated (GHT) with a specific TxA2-PGH2 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 pressor agents compared with SC rats. Chronic TxA2-PGH2 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, TxA2-PGH2 blockade normalizes BP through decreasing the vascular responsiveness to the main pressor agents. In malignant forms, it limits the elevation of BP and markedly reduces mortality.
1. The effects of CGS 22652, a thromboxane (Tx) A2 synthase inhibitor and TxA2/prostaglandin (PG) H2 receptor antagonist, on blood pressure (BP) were studied in conscious freely moving spontaneously hypertensive rats (SHR). 2. Three groups of 13 male SHR were subcutaneously infused from 5 to 11 weeks of age via osmotic minipumps with CGS 22652 at doses of 5 (SHRa) or 10 (SHRb) mg/kg per 24 h or with the vehicle only (SHRc). A fourth group (SHRd, n = 13) was orally treated from 3 to 11 weeks of age with CGS 22652 (30 mg/kg) given by gavage once a day. 3. CGS 22652 dose-dependently reduced the age-related increase in systolic BP. The pressor response to noradrenaline (200 ng/kg, i.v.) but not to angiotensin I or II was slightly (P < 0.05) diminished in 11 week old SHRb and SHRd compared to SHRc. Acute ganglionic blockade by trimethaphan (10 mg/kg, i.v.), as well as angiotensin converting enzyme inhibition by perindopril (2 mg/kg, i.v.) decreased BP to a similar extent in the four groups. After combined blockade of vasopressin receptors and of the autonomic nervous system and the administration of a direct vasodilator (hydralazine, 3 mg/kg, i.v.), the residual mean BP was identical in the four groups of rats. 4. Chronic treatment with CGS 22652 dose-dependent antagonized the TxA2/PGH2 receptors but did not modify the TxA2 synthesis. The urinary sodium excretion did not differ between groups. 5. In conclusion, at the doses used, CGS 22652 given either orally or subcutaneously exhibited only TxA2/PGH2 receptor blocking properties in SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
The effects on blood pressure (BP) of a single and repeated renal denervations (RD) were compared in genetically hypertensive (LH) and normotensive (LN) rats of the Lyon strain. Indirect BP was measured by the tail-cuff method, and direct BP was measured through an aortic catheter in conscious quiet rats receiving a normal-sodium diet. Single RD (10 wk of age) did not reduce BP in both LN and LH rats. Repeated RD (4, 7, and 10 wk of age) partly prevented the age-related increase in tail-cuff BP but did not affect the directly recorded BP in 11-wk-old LH rats. Single and repeated RD reduced the renal norepinephrine content by greater than 90%. Both procedures did not alter the BP lowering effects of angiotensin-converting enzyme inhibition and of ganglionic blockade. It is concluded that renal nerves are not necessary for the development and the maintenance of hypertension in LH rats.
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