Thromboxane inhibition potentiates antihypertensive effects of alpha 1 adrenoceptor antagonists in the rat

Prostaglandins Leukot Essent Fatty Acids. 1997 Feb;56(2):127-34. doi: 10.1016/s0952-3278(97)90509-3.

Abstract

We investigated the influence of the vascular and renal thromboxane system on the antihypertensive effects of the alpha 1 adrenoceptor antagonist (alpha 1 blocker) bunazosin in spontaneously hypertensive rats (SHR). SHR were treated for 2 weeks with the alpha 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 A2 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 alpha 1 blocker. Such synergy was also observed between OKY-046 and prazosin, an alternative alpha 1 blocker, but not with amosulalol, an alpha 1 blocker having no quinazoline moiety. alpha 1 blockers with a quinazoline moiety dose-dependently stimulate thromboxane generation in cultured smooth muscle cells from SHR. These data indicate that alpha 1 blockers enhance thromboxane generation in the arterial wall and kidney, thereby contributing to the lessening of the antihypertensive effects observed during alpha 1 blocker treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology*
  • Animals
  • Antihypertensive Agents / pharmacology*
  • Aorta
  • Blood Pressure / drug effects*
  • Body Weight / drug effects
  • Cells, Cultured
  • Drug Synergism
  • Eicosanoids / metabolism
  • Eicosanoids / urine
  • Ethanolamines / pharmacology
  • Kidney / drug effects
  • Kidney / metabolism
  • Methacrylates / pharmacology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Prazosin / pharmacology
  • Quinazolines / pharmacology
  • Rats
  • Rats, Inbred SHR
  • Sodium / metabolism
  • Sodium / urine
  • Thromboxane-A Synthase / antagonists & inhibitors
  • Thromboxanes / antagonists & inhibitors*
  • Thromboxanes / metabolism

Substances

  • Adrenergic alpha-Antagonists
  • Antihypertensive Agents
  • Eicosanoids
  • Ethanolamines
  • Methacrylates
  • Quinazolines
  • Thromboxanes
  • Sodium
  • bunazosin
  • amosulalol
  • Thromboxane-A Synthase
  • ozagrel
  • Prazosin