thromboxane-a2 and bunazosin

In order to assess the roles of vasoconstrictor thromboxane in the antihypertensive action of alpha 1 adrenoceptor antagonist, we explored the influences of OKY-046, a selective thromboxane inhibitor, on the antihypertensive effects of bunazosin in spontaneously hypertensive rats (SHR). 2-week antihypertensive treatment with bunazosin (0.5 mg/kg/day) did not produce a significant decrease of systolic blood pressure in SHR, as compared to untreated controls. The blood pressure reduction was associated with a decrease of PGI2/TXA2 in vascular eicosanoids generation (p less than 0.02) and an increase of TXA2 excretion in urine (p less than 0.05). A combination treatment with OKY-046 almost completely abolished the enhanced TXA2 generation in the vascular wall and kidney, which was strikingly associated with a potentiation of the blood pressure reduction by bunazosin treatment (176 vs 186 mmHg, p less than 0.01). Bunazosin directly stimulated TXA2 biosynthesis in vascular smooth muscle cells in culture in a dose-dependent manner. Thus, these data clearly indicate that bunazosin, a quinazoline derivative, enhances vasoconstrictor TXA2 system in the vascular wall and kidney possibly through direct actions, which would attenuate the antihypertensive effects of alpha 1 adrenoceptor antagonism by bunazosin treatment.

Topics: Adrenergic alpha-Antagonists; Animals; Blood Vessels; Hypertension; Kidney; Male; Methacrylates; Quinazolines; Rats; Rats, Inbred SHR; Thromboxane A2; Thromboxane-A Synthase