Role of thromboxane A2 in the hypotensive effect of captopril in essential hypertension

K. Kudo, K. Abe, S. Chiba, M. Sato, M. Yasujima, M. Kohzuki, K. Omata, M. Tanno, K. Tsunoda, K. Yoshinaga

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18 Citations (Scopus)

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 < 0.01) and increased urinary sodium excretion significantly (from 73.0 ± 15.3 to 113.0 ± 14.4 μEq/min; p < 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 < 0.001) and a significant decrease in mean arterial pressure (from 97.0 ± 4.7 to 88.1 ± 5.1 mm Hg; p < 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 < 0.01) and in mean arterial pressure (from 105.1 ± 3.8 to 84.2 ± 3.6 mm Hg; p < 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 F(1α) excretion in response to captopril. These results indicate that thromboxane A2 counteracts the hypotensive effect of captopril in patients with essential hypertension.

Original languageEnglish
Pages (from-to)147-152
Number of pages6
JournalHypertension
Volume11
Issue number2
DOIs
Publication statusPublished - 1988

ASJC Scopus subject areas

  • Internal Medicine

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