Effect of Ifetroban, a Thromboxane a₂ Receptor Antagonist, in Stroke-Prone Spontaneously Hypertensive Rats

Abstract

Experiments were performed to determine the effect of chronic therapy with the potent and long-acting thromboxane (TX) A₂/prostaglandin endoperoxide (TP) receptor antagonist, ifetroban, on hypertension development and the incidence of stroke in stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP instrumented with radiotelemetry probes, for continuous monitoring of arterial blood pressure, were given 1% NaCl to drink and Stroke-Prone Rodent Diet and were chronically treated with ifetroban (20 mg/kg/day, n=l0) or vehicle (n=12) starting at 16.5 weeks of age. Ifetroban did not affect blood pressure or the development of proteinuria and cerebrovascular lesions, Chronic administration of a higher dose ifetroban (40mg/kg/day) starting at 7 weeks of age was also without effect on blood pressure and stroke in noninstrumented saline-drinking SHRSP. These results do not support a major role for TXA, and its endoperoxide precursors in the elevation of blood pressure and the development of cerebrovascular lesions in saline-drinking SHRSP.

Key Words:

• Blood pressure
• stroke-prone spontaneously hypertensive rats
• thromboxane receptor antagonist ifetroban