Thromboxane A2 does not mediate angiotensin II-dependent nonischemic peripheral vasoconstriction in healthy men: a pilot study.
It has been suggested that angiotensin II-dependent hemodynamic effects are in part mediated by thromboxane A2 (TXA2). The present study investigates in 6 healthy normotensive men whether prostaglandin H2-TXA2 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 B2 (TXB2), a stable metabolite of TXA2, across the leg vascular bed was assessed at baseline conditions as well as during exogenous infusion (0.2 microgram/min) of angiotensin II. Net transfemoral TXB2 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 microgram/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 H2-TXA2 receptor blockade. Baseline TXB2 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 TXA2. Possible benefits of prostaglandin H2-TXA2 receptor blockade in pathological conditions with tissue malperfusion or ischemia are discussed.
Gasic
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S
Hafslund Nycomed Pharma AG, Linz, Austria.
Eichler
H G
HG
Kyrle
P A
PA
Wolzt
M
M
Eidenberger
T
T
Vierhapper
H
H
D000328:Adult; D000804:Angiotensin II / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007866:Leg / Q000098:blood supply; D008297:Male; D010865:Pilot Projects; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D012039:Regional Blood Flow / Q000187:drug effects; D013928:Thromboxane A2 / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology*
D017482:Receptors, Thromboxane; D000804:Angiotensin II; D013928:Thromboxane A2