THROMBOXANE INHIBITION POTENTIATES ANTIHYPERTENSIVE EFFECTS OF ALPHA(1) ADRENOCEPTOR ANTAGONISTS IN THE RAT

We investigated the influence of the vascular and renal thromboxane sy stem on the antihypertensive effects of the alpha(1) adrenoceptor anta gonist (alpha(1) blocker) bunazosin in spontaneously hypertensive rats (SHR). SHR were treated for 2 weeks with the alpha(1) blocker bunazos in (0.5 mg/kg body weight/day). The systolic blood pressure immediatel y declined with bunazosin treatment, and then rose toward the level ob served in untreated SHR. This antihypertensive effect was accompanied by a decrease in the ratio of prostacyclin to thromboxane A(2) in the vascular wall and the kidney. A subdepressor dose of the thromboxane s ynthase inhibitor OKY-046 lessened the thromboxane generation during b unazosin treatment, and synergistically potentiated the antihypertensi ve action of the alpha(1) blocker. Such synergy was also observed betw een OKY-046 and prazosin, an alternative alpha(1) blocker, but not wit h amosulalol, an alpha(1) blocker having no quinazoline moiety. alpha( 1) blockers with a quinazoline moiety dose-dependently stimulate throm boxane generation in cultured smooth muscle cells from SHR. These data indicate that alpha(1) blockers enhance thromboxane generation in the arterial wail and kidney, thereby contributing to the lessening of th e antihypertensive effects observed during alpha(1) blocker treatment.