Direct evidence that thromboxane mimetic U44069 preferentially constricts the afferent arteriole

Koichi Hayashi, Rodger Loutzenhiser, Murray Epstein

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Abstract

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.

Original languageEnglish
Pages (from-to)25-31
Number of pages7
JournalJournal of the American Society of Nephrology
Volume8
Issue number1
Publication statusPublished - 1997 Jan

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Thromboxanes
Arterioles
Thromboxane A2
Constriction
Diltiazem
Kidney
Prostaglandin H2 Receptors Thromboxane A2
Calcium
Nifedipine
Microvessels
Vasodilator Agents
U 44069
Hemodynamics

ASJC Scopus subject areas

  • Nephrology

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Direct evidence that thromboxane mimetic U44069 preferentially constricts the afferent arteriole. / Hayashi, Koichi; Loutzenhiser, Rodger; Epstein, Murray.

In: Journal of the American Society of Nephrology, Vol. 8, No. 1, 01.1997, p. 25-31.

Research output: Contribution to journalArticle

Hayashi, Koichi ; Loutzenhiser, Rodger ; Epstein, Murray. / Direct evidence that thromboxane mimetic U44069 preferentially constricts the afferent arteriole. In: Journal of the American Society of Nephrology. 1997 ; Vol. 8, No. 1. pp. 25-31.
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abstract = "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.",
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