Vasoconstrictor responses in thromboxane receptor knockout mice: tubuloglomerular feedback and ureteral obstruction

The role of thromboxane (TP) in the vasoconstriction induced by tubuloglome rular feedback or 18-h ureteral obstruction was studied in wild type mice ( TP +/+), and in heterozygous (TP +/-) and homozygous TP receptor knockout m ice (TPR -/-). TGF function was assessed from the response of stop flow pre ssure (P-SF) to a maximum increase in loop of Henle flow rate (0-30 nL min( -1)). P-SF fell by 6.4 +/- 0.4 mmHg in wild-type mice, by 6.1 +/- 0.6 mmHg in TP +/-, and by 7.9 +/- 0.7 mmHg in TP -/- mice. In the presence of the T P receptor agonist U46,619 (10(-5) M) the P-SF reduction increased to 10.4 +/- 0.8 mmHg in TP +/+, and to 10.6 +/- 2.8 mmHg in TP +/-, but was unchang ed at 7.7 +/- 0.7 mmHg in TP -/-. Mean arterial blood pressures were compar able between groups (103 +/- 3 mmHg in TP +/+, 113 +/- 4.6 in TP +/- and 11 3 +/- 2.4 mmHg in TP -/- mice). Intratubular pressure following unilateral ureteral obstruction was significantly higher in TP -/- than in TP +/+ mice both in the early phase (0-3 h) and late phase (18 h) of obstruction. Thes e results indicate that chronic TP receptor deficiency does not significant ly alter maximum TGF responses in mice, and that it is accompanied by exagg erated vasodilatation during short-term unilateral ureteral obstruction and attenuated vasoconstriction during longer lasting obstruction. We conclude that thromboxane is primarily a regulator of renal vascular tone under pat hophysiological conditions.