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 = 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.

• Authors: R A Johnson, A Belmonte, N Y Fan, M Lavesa, A Nasjletti, C T Stier Jr
• Journal: Clinical and experimental hypertension (New York, N.Y. : 1993) (Clin Exp Hypertens) Vol. 18 Issue 2 Pg. 171-88 (Feb 1996) ISSN: 1064-1963 [Print] England
• PMID: 8868999 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Bridged Bicyclo Compounds, Heterocyclic
• Oxazoles
• Receptors, Thromboxane
• ifetroban

Topics

• Animals
• Bridged Bicyclo Compounds, Heterocyclic (pharmacology)
• Cerebrovascular Disorders (epidemiology, genetics)
• Genetic Predisposition to Disease
• Hypertension (genetics)
• Incidence
• Male
• Oxazoles (pharmacology)
• Rats
• Rats, Inbred SHR (genetics)
• Receptors, Thromboxane (antagonists & inhibitors)
• Survival Analysis
• Telemetry