title: Role of thromboxane A2 in the hypotensive effect of captopril in essential hypertension.
abstract: We have previously reported that captopril stimulates thromboxane A2 synthesis in patients with essential hypertension. In the present study, the hypotensive effects of captopril and OKY-046, a selective inhibitor of thromboxane A2 synthetase, were studied in nine patients with essential hypertension to determine whether thromboxane A2 is involved in the regulation of blood pressure. A single oral dose of OKY-046 (400 mg) decreased urinary thromboxane B2 (a stable metabolite of thromboxane A2) excretion significantly (from 113 +/- 19.0 to 51.0 +/- 6.1 pg/min; p less than 0.01) and increased urinary sodium excretion significantly (from 73.0 +/- 15.3 to 113.0 +/- 14.4 microEq/min; p less than 0.01), but no change was observed in mean arterial pressure. The administration of OKY-046 (600 mg/day) for 3 days induced a significant and sustained decrease in urinary thromboxane B2 excretion, but it did not affect the mean arterial pressure. Although captopril (50 mg) alone induced a significant increase in urinary thromboxane B2 excretion (from 91.4 +/- 11.0 to 297.3 +/- 30.8 pg/min; p less than 0.001) and a significant decrease in mean arterial pressure (from 97.0 +/- 4.7 to 88.1 +/- 5.1 mm Hg; p less than 0.01), captopril in combination with OKY-046 induced a decrease both in urinary thromboxane B2 excretion (from 70.8 +/- 12.3 to 54.2 +/- 14.7 pg/min; p less than 0.01) and in mean arterial pressure (from 105.1 +/- 3.8 to 84.2 +/- 3.6 mm Hg; p less than 0.01). Thus, the hypotensive effect of captopril was potentiated by OKY-046. OKY-046 did not affect the changes in plasma renin activity and plasma aldosterone concentration and blunted urinary prostaglandin E2 and 6-keto-prostaglandin F1 alpha excretion in response to captopril. These results indicate that thromboxane A2 counteracts the hypotensive effect of captopril in patients with essential hypertension.
authors.affiliation: Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kudo
authors.forename: K
authors.initials: K
authors.lastname: Abe
authors.forename: S
authors.initials: S
authors.lastname: Chiba
authors.forename: M
authors.initials: M
authors.lastname: Sato
authors.forename: M
authors.initials: M
authors.lastname: Yasujima
authors.forename: M
authors.initials: M
authors.lastname: Kohzuki
authors.forename: K
authors.initials: K
authors.lastname: Omata
authors.forename: M
authors.initials: M
authors.lastname: Tanno
authors.forename: K
authors.initials: K
authors.lastname: Tsunoda
authors.forename: K
authors.initials: K
authors.lastname: Yoshinaga
mesh_terms: D000328:Adult; D001794:Blood Pressure; D002216:Captopril / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008689:Methacrylates; D013928:Thromboxane A2 / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
chemical_list: D008689:Methacrylates; D013928:Thromboxane A2; D002216:Captopril; D013930:Thromboxane-A Synthase; C034364:ozagrel