BLOOD PRESSURE EFFECTS OF THROMBOXANE A2 BLOCKADE IN SPONTANEOUSLY HYPERTENSIVE RATS

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-dependently 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. Chronic treatment modestly prevented the development of hypertension in SHR, probably through a decrease in the pressor effects of TxA₂ and of noradrenaline.