Jpn. J. Pharmacol. 78 (4), 479-486 (1998)

Effects of Ridogrel, a Thromboxane Synthase Inhibitor and Receptor Antagonist, on Blood Pressure in the Spontaneously Hypertensive Rat

Dale W. Quest and Thomas W. Wilson (*)

Cardiovascular Risk Factor Reduction Unit (C.R.F.R.U.), Department of Medicine, Division of Clinical Pharmacology, Royal University Hospital, 103 Hospital Drive, Saskatoon, SK, Canada, S7N OW8
(*) To whom correspondence should be addressed.

Abstract: Ridogrel is a dual acting thromboxane synthase inhibitor/TP receptor antagonist. We examined the effects of single and multiple doses on systolic blood pressure in stroke-prone spontaneously hypertensive rats. Single doses of ridogrel (5 to 125 mg/kg) did not affect systolic blood pressure or furosemide-stimulated excretion rates of thromboxane B2 or 6-keto-prostaglandin F1alpha although ex vivo serum thromboxane B2 was dose-dependently reduced up to 95%. In contrast, repeated dosing (7 days) with ridogrel (3 to 25 mg/kg/day), had an antihypertensive effect in 12-week-old stroke-prone spontaneously hypertensive rats. At 25 mg/kg/day, ridogrel reduced systolic blood pressure from 200+/-6.1 to 173+/-6.7 mmHg (n=12, P<0.01). Ridogrel dose-dependently reduced serum thromboxane B2 and increased plasma renin activity. Unlike single doses, repeated dosing reduced urinary thromboxane B2 excretion (from 103+/-7 ng/day to 49+/-1O ng/day, P<0.01) while preserving 6-keto-prostaglandin F1alpha excretion. Ketoprofen, a cyclo-oxygenase inhibitor, (10 mg/kg/day for 7 days), depressed urine 6-keto-prostaglandin F1alpha in addition to attenuating serum and urine thromboxane B2. Ketoprofen prevented the antihypertensive effects of ridogrel. Ridogrel did not lower systolic blood pressure in Sprague-Dawley rats. We conclude that the antihypertensive effect of ridogrel involves preserving renal prostaglandin synthesis during thromboxane attenuation.

Keywords: Blood pressure, Renal prostanoid, Ridogrel, Thromboxane

Copyrightę The Japanese Pharmacological Society 1998

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