Effect of ifetroban, a thromboxane A2 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) 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 = 10) 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 (40 mg/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 TXA2 and its endoperoxide precursors in the elevation of blood pressure and the development of cerebrovascular lesions in saline-drinking SHRSP.
Johnson
R A
RA
Department of Pharmacology, New York Medical College, Valhalla 10595, USA.
Belmonte
A
A
Fan
N Y
NY
Lavesa
M
M
Nasjletti
A
A
Stier
C T
CT
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002561:Cerebrovascular Disorders / Q000453:epidemiology* / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006973:Hypertension / Q000235:genetics*; D015994:Incidence; D008297:Male; D010080:Oxazoles / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D016019:Survival Analysis; D013686:Telemetry
D019086:Bridged Bicyclo Compounds, Heterocyclic; D010080:Oxazoles; D017482:Receptors, Thromboxane; C078904:ifetroban