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Effects of OKY-046, a selective thromboxane synthetase inhibitor, on blood pressure and thromboxane synthesis in spontaneously hypertensive rats.
Prostaglandins Leukot Essent Fatty Acids. 1989 Sep; 37(3):139-44.PL

Abstract

The effects of OKY-046, a specific thromboxane (TX) synthetase inhibitor, on blood pressure, urinary TX excretion, TX synthesis in blood platelets, kidney slices and aortic strips, were evaluated in adult spontaneously hypertensive rats (SHR). OKY-046 was dissolved in drinking water at concentrations of 1, 10, 100 mg/dl. The average intakes of OKY-046 were 1.4 +/- 0.1, 13.0 +/- 1.1, and 147 +/- 12 mg/kg/day, in rats who took 1, 10, 100 mg/dl of OKY-046 solutions for drinking water, respectively. The systolic blood pressure was significantly decreased by 34 mmHg only with the high dose of OKY-046 (147 mg/kg/day). OKY-046 suppressed the platelet aggregability to ADP and the release of TX B2, a stable metabolite of TX A2, from blood platelets in a dose-dependent fashion. Urinary excretion of TX B2 decreased significantly in both groups treated with moderate (13.0 mg/kg/day) and high doses of OKY-046 (147 mg/kg/day). The release of TX B2 from kidney slices was decreased only by the high dose of OKY-046, while the release of TX B2 from aortic strips was not changed even by the high dose of OKY-046. OKY-046 had no effect on urinary excretion of 6-keto-prostaglandin F1 alpha, a stable metabolite of prostacyclin, or, on its release from the kidney slices and aortic strips. These results suggest that the effect of OKY-046 on TX synthesis has organ specificity and that the antihypertensive effect of this drug in SHR is related to reduced renal TX synthesis.

Authors+Show Affiliations

Department of Nephrology, Kanto-Teishin Hospital, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

2608692

Citation

Gomi, T, et al. "Effects of OKY-046, a Selective Thromboxane Synthetase Inhibitor, On Blood Pressure and Thromboxane Synthesis in Spontaneously Hypertensive Rats." Prostaglandins, Leukotrienes, and Essential Fatty Acids, vol. 37, no. 3, 1989, pp. 139-44.
Gomi T, Ikeda T, Ishimitsu T, et al. Effects of OKY-046, a selective thromboxane synthetase inhibitor, on blood pressure and thromboxane synthesis in spontaneously hypertensive rats. Prostaglandins Leukot Essent Fatty Acids. 1989;37(3):139-44.
Gomi, T., Ikeda, T., Ishimitsu, T., & Uehara, Y. (1989). Effects of OKY-046, a selective thromboxane synthetase inhibitor, on blood pressure and thromboxane synthesis in spontaneously hypertensive rats. Prostaglandins, Leukotrienes, and Essential Fatty Acids, 37(3), 139-44.
Gomi T, et al. Effects of OKY-046, a Selective Thromboxane Synthetase Inhibitor, On Blood Pressure and Thromboxane Synthesis in Spontaneously Hypertensive Rats. Prostaglandins Leukot Essent Fatty Acids. 1989;37(3):139-44. PubMed PMID: 2608692.
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TY - JOUR T1 - Effects of OKY-046, a selective thromboxane synthetase inhibitor, on blood pressure and thromboxane synthesis in spontaneously hypertensive rats. AU - Gomi,T, AU - Ikeda,T, AU - Ishimitsu,T, AU - Uehara,Y, PY - 1989/9/1/pubmed PY - 1989/9/1/medline PY - 1989/9/1/entrez SP - 139 EP - 44 JF - Prostaglandins, leukotrienes, and essential fatty acids JO - Prostaglandins Leukot Essent Fatty Acids VL - 37 IS - 3 N2 - The effects of OKY-046, a specific thromboxane (TX) synthetase inhibitor, on blood pressure, urinary TX excretion, TX synthesis in blood platelets, kidney slices and aortic strips, were evaluated in adult spontaneously hypertensive rats (SHR). OKY-046 was dissolved in drinking water at concentrations of 1, 10, 100 mg/dl. The average intakes of OKY-046 were 1.4 +/- 0.1, 13.0 +/- 1.1, and 147 +/- 12 mg/kg/day, in rats who took 1, 10, 100 mg/dl of OKY-046 solutions for drinking water, respectively. The systolic blood pressure was significantly decreased by 34 mmHg only with the high dose of OKY-046 (147 mg/kg/day). OKY-046 suppressed the platelet aggregability to ADP and the release of TX B2, a stable metabolite of TX A2, from blood platelets in a dose-dependent fashion. Urinary excretion of TX B2 decreased significantly in both groups treated with moderate (13.0 mg/kg/day) and high doses of OKY-046 (147 mg/kg/day). The release of TX B2 from kidney slices was decreased only by the high dose of OKY-046, while the release of TX B2 from aortic strips was not changed even by the high dose of OKY-046. OKY-046 had no effect on urinary excretion of 6-keto-prostaglandin F1 alpha, a stable metabolite of prostacyclin, or, on its release from the kidney slices and aortic strips. These results suggest that the effect of OKY-046 on TX synthesis has organ specificity and that the antihypertensive effect of this drug in SHR is related to reduced renal TX synthesis. SN - 0952-3278 UR - https://www.unboundmedicine.com/medline/citation/2608692/Effects_of_OKY_046_a_selective_thromboxane_synthetase_inhibitor_on_blood_pressure_and_thromboxane_synthesis_in_spontaneously_hypertensive_rats_ L2 - https://medlineplus.gov/bloodpressuremedicines.html DB - PRIME DP - Unbound Medicine ER -