Direct evidence that thromboxane mimetic U44069 preferentially constricts the afferent arteriole

The thromboxane A₂ (TXA₂) 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 preglomerular vessels. To assess this possibility directly, effects of U44069 on the renal microvessels of the isolated perfused hydronephrotic kidney were examined. At 10^-6 mol/L, U44069 elicited a 27 ± 2% decrease in afferent arteriolar (AA) diameter (from 18.8 ± 0.3 to 13.7 ± 0.3 μm, P < 0.001). In contrast, efferent arteriolar (EA) diameter decreased by only 9 ± 1% (from 16.4 ± 0.5 to 15.0 ± 0.5 μm, P < 0.001). These effects on both AA and EA were completely reversed by the TXA₂ receptor antagonist SQ29548. The calcium antagonist diltiazem reversed U44069-induced AA constriction by 83 ± 5%. The U44069-induced EA constriction was insensitive to the vasodilator action of diltiazem at concentrations from 10^-8 to 10^-6 mol/L, but at 10^-5 mol/L, diltiazem increased the EA diameter significantly, albeit modestly. 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 evidence that a TXA₂ agonist preferentially constricts the afferent arteriole. Furthermore, the ability of both the calcium antagonist and SQ29548 to reverse the renal microvascular actions of TXA₂ agonists suggests a potential utility of these agents in ameliorating TXA₂-induced renal hemodynamic abnormalities.