Thromboxane inhibition potentiates antihypertensive effects of α1 adrenoceptor antagonists in the rat

Abstract We investigated the influence of the vascular and renal thromboxane system on the antihypertensive effects of the α 1 adrenoceptor antagonist ( α 1 blocker) bunazosin in spontaneously hypertensive rats (SHR). SHR were treated for 2 weeks with the α 1 blocker bunazosin (0.5 mg/kg body weight/day). The systolic blood pressure immediately declined with bunazosin treatment, and then rose toward the level observed 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 synthase inhibitor OKY-046 lessened the thromboxane generation during bunazosin treatment, and synergistically potentiated the antihypertensive action of the α 1 blocker. Such synergy was also observed between OKY-046 and prazosin, an alternative α 1 blocker, but not with amosulalol, an α 1 blocker having no quinazoline moiety. α 1 blockers with a quinazoline moiety dose-dependently stimulate thromboxane generation in cultured smooth muscle cells from SHR. These data indicate that α 1 blockers enhance thromboxane generation in the arterial wall and kidney, thereby contributing to the lessening of the antihypertensive effects observed during α 1 blocker treatment.