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 B 2, a stable metabolite of TX A 2, from blood platelets in a dose-dependent fashion. Urinary excretion of TX B 2 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 B 2 from kidney slices was decreased only by the high dose of OKY-046, while the release of TX B 2 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 F 1α, 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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
More From: Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA)
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.