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

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Author(s)

    • Quest Dale W. QUEST Dale W.
    • Cardiovascular Risk Factor Reduction Unit (C.R.F.R. U.), Department of Medicine, Division of Clinical Pharmacology,Royal University Hospital
    • Wilson Thomas W. WILSON Thomas W.
    • Cardiovascular Risk Factor Reduction Unit (C.R.F.R. U.), Department of Medicine, Division of Clinical Pharmacology,Royal University Hospital

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 B<SUB>2</SUB> or 6-keto-prostaglandin F<SUB>1α</SUB>, although ex vivo serum thromboxane B<SUB>2</SUB> 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 B<SUB>2</SUB> and increased plasma renin activity. Unlike single doses, repeated dosing reduced urinary thromboxane B<SUB>2</SUB> excretion (from 103±7 ng/day to 49±10 ng/day, P<0.01) while preserving 6-keto-prostaglandin F<SUB>1α</SUB> excretion. Ketoprofen, a cyclo-oxygenase inhibitor, (10 mg/kg/day for 7 days), depressed urine 6-keto-prostaglandin F<SUB>1α</SUB> in addition to attenuating serum and urine thromboxane B<SUB>2</SUB>. 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.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 78(4), 479-486, 1998-12-01

    The Japanese Pharmacological Society

References:  52

Codes

  • NII Article ID (NAID)
    10008681847
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00215198
  • NDL Article ID
    4629553
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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