It has been suggested that angiotensin II-dependent hemodynamic effects are in part mediated by thromboxane A 2 (TXA 2). The present study investigates in 6 healthy normotensive men whether prostaglandin H 2-TXA 2 receptor blockade with 100 mg of linotroban (5(2-(phenylsulfonylamino)ethyl)-thienyloxy-acetic acid) p.o. influences angiotensin II-dependent peripheral regional vasoconstriction. Moreover, the regional balance of thromboxane B 2 (TXB 2), a stable metabolite of TXA 2, across the leg vascular bed was assessed at baseline conditions as well as during exogenous infusion (0.2 μg/min) of angiotensin II. Net transfemoral TXB 2 balance was calculated from the respective arteriovenous plasma concentration differences and the corresponding regional plasma flow, the latter being determined by indocyanine-green dye, using appropriate catheterization techniques. Angiotensin II (0.2 ug/min) induced a 66% increase in leg vascular resistance (p < 0.01) without affecting systemic hemodynamics. These regional hemodynamic effects of angiotensin II were not influenced by prostaglandin H 2-TXA 2 receptor blockade. Baseline TXB 2 balance across the femoral vascular bed was equilibrated at slight extraction rates or around zero and remained unchanged during angiotensin II infusion. These results suggest that, in healthy man, angiotensin II-dependent, nonischemic peripheral vasoconstriction is not mediated by TXA 2. Possible benefits of prostaglandin H 2-TXA 2 receptor blockade in pathological conditions with tissue malperfusion or ischemia are discussed.
|Seiten (von - bis)||56-60|
|Fachzeitschrift||International Journal of Clinical Pharmacology and Therapeutics|
|Publikationsstatus||Veröffentlicht - Feb. 1997|