Angiotensin II and thromboxane in the regulation of blood pressure and renal function

In experiments in anesthetized rats, the hypothesis that angiotensin II (Ang II) infusion released thromboxane (TxA2) which modulated the systemic and renal vasoconstriction was tested. Intravenous Ang II (500 ng.kg-1.min-1) increased MAP by 35 +/- 3 mm Hg and the excretion of TxB2 (P less than 0.03), whereas a similar pressor infusion of phenylephrine did not increase TxB2 excretion. A TxA2 receptor antagonist (TxRA) SQ-29,548 (8 mg.kg-1.hr-1) or pretreatment with a thromboxane synthesis inhibitor (TSI), UK-38,485 (50 mg.kg-1.day-1 x 3) blunted (P less than 0.005) the pressor response to 12 +/- 2 and 11 +/- 2 mm Hg, respectively, whereas TxRA did not modify the pressor response to phenylephrine. Infusion of Ang II at a dose of 50 ng.kg-1.min-1 reduced the GFR and increased the filtration fraction and renal vascular resistance. TxRA blunted (P less than 0.01) these effects of Ang II.

1.) Ang II releases TxA2 within the kidney independent of hypertension; 2.) TxA2 can mediate much of the pressor and renal hemodynamic responses to Ang II.