[Roles of vascular and renal thromboxanes in the antihypertensive effects of alpha 1 adrenoceptor antagonists].
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.
Takada
S
S
Uehara
Y
Y
Hirawa
N
N
Numabe
A
A
Yagi
S
S
D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy*; D007668:Kidney / Q000378:metabolism; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D011799:Quinazolines / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D013928:Thromboxane A2 / Q000096:biosynthesis / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D000317:Adrenergic alpha-Antagonists; D008689:Methacrylates; D011799:Quinazolines; D013928:Thromboxane A2; C018176:bunazosin; D013930:Thromboxane-A Synthase; C034364:ozagrel