EFFECT OF IFETROBAN, A THROMBOXANE A(2) RECEPTOR ANTAGONIST, IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

Experiments were performed to determine the effect of chronic therapy with the potent and long-acting thromboxane (TX) A(2)/prostaglandin en doperoxide (TP) receptor antagonist, ifetroban, on hypertension develo pment and the incidence of stroke in stroke-prone spontaneously hypert ensive rats (SHRSP). SHRSP instrumented with radiotelemetry probes, fo r continuous monitoring of arterial blood pressure, were given 1% NaCl to drink and Stroke-Prone Rodent Diet and were chronically treated wi th ifetroban (20 mg/kg/day, n=10) or vehicle (n=12) starting at 16.5 w eeks of age. Ifetroban did not affect blood pressure or the developmen t of proteinuria and cerebrovascular lesions. Chronic administration o f a higher dose ifetroban (40mg/kg/day) starting at 7 weeks of age was also without effect on blood pressure and stroke in noninstrumented s aline-drinking SHRSP. These results do not support a major role for TX A(2) and its endoperoxide precursors in the elevation of blood pressur e and the development of cerebrovascular lesions in saline-drinking SH RSP.