DIRECT EVIDENCE THAT THROMBOXANE MIMETIC U44069 PREFERENTIALLY CONSTRICTS THE AFFERENT ARTERIOLE

The thromboxane A(2) (TXA(2)) mimetic U44069 has been demonstrated to reduce the GFR and filtration fraction of the normal isolated perfused rat kidney markedly, suggesting a predominant constriction of preglom erular vessels. To assess this possibility directly, effects of U44069 on the renal microvessels of the isolated perfused hydronephrotic kid ney were examined. At 10(-6) mol/L, U44069 elicited a 27 +/- 2% decrea se in afferent arteriolar (AA) diameter (from 18.8 +/- 0.3 to 13.7 +/- 0.3 mu m, P < 0.001). In contrast, efferent arteriolar (EA) diameter decreased by only 9 +/- 1% (from 16.4 +/- 0.5 to 15.0 +/- 0.5 mu m, P < 0.001). These effects on both AA and EA were completely reversed by the TXA(2) receptor antagonist S429548. The calcium antagonist diltiaz em reversed U44069-induced AA constriction by 83 +/- 5%. The U44069-in duced EA constriction was insensitive to the vasodilator action of dil tiazem at concentrations from 10(-8) to 10(-6) mol/L, but at 10(-5) mo l/L, diltiazem increased the EA diameter significantly, albeit modestl y. Nifedipine also reversed the U44069-induced AA constriction (81 +/- 7%), but failed to inhibit the EA constriction at concentrations from 10(-9) to 10(-6) mol/L. These findings constitute the first direct ev idence that a TXA(2) agonist preferentially constricts the afferent ar teriole. Furthermore, the ability of both the calcium antagonist and S Q29548 to reverse the renal microvascular actions of TXA(2) agonists s uggests a potential utility of these agents in ameliorating TXA(2)-ind uced renal hemodynamic abnormalities.