Thromboxane inhibition potentiates antihypertensive effects of alpha 1 adrenoceptor antagonists in the rat.
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.
Takada
S
S
Department of Medicine, Dokkyo University School of Medicine, Mibu, Japan.
Numabe
A
A
Hirawa
N
N
Yagi
S
S
Uehara
Y
Y
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001011:Aorta; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D015777:Eicosanoids / Q000378:metabolism / Q000652:urine; D004983:Ethanolamines / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008689:Methacrylates / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D011224:Prazosin / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D012964:Sodium / Q000378:metabolism / Q000652:urine; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D013931:Thromboxanes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000096926:Benzenesulfonamides
D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D015777:Eicosanoids; D004983:Ethanolamines; D008689:Methacrylates; D011224:Prazosin; D011799:Quinazolines; D012964:Sodium; D013930:Thromboxane-A Synthase; D013931:Thromboxanes; C018176:bunazosin; C032473:amosulalol; D000096926:Benzenesulfonamides; C034364:ozagrel