Vasoconstrictor responses in thromboxane receptor knockout mice: tubuloglomerular feedback and ureteral obstruction.
The role of thromboxane (TP) in the vasoconstriction induced by tubuloglomerular feedback or 18-h ureteral obstruction was studied in wild type mice (TP +/+), and in heterozygous (TP +/-) and homozygous TP receptor knockout mice (TPR -/-). TGF function was assessed from the response of stop flow pressure (PSF) to a maximum increase in loop of Henle flow rate (0-30 nL min-1). PSF 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 TP receptor agonist U46,619 (10-5 M) the PSF reduction increased to 10. 4 +/- 0.8 mmHg in TP +/+, and to 10.6 +/- 2.8 mmHg in TP +/-, but was unchanged at 7.7 +/- 0.7 mmHg in TP -/-. Mean arterial blood pressures were comparable between groups (103 +/- 3 mmHg in TP +/+, 113 +/- 4.6 in TP +/- and 113 +/- 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. These results indicate that chronic TP receptor deficiency does not significantly alter maximum TGF responses in mice, and that it is accompanied by exaggerated 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 pathophysiological conditions.
Schnermann
J
J
National Institute of Diabetes, Digestive, and Kidney Diseases, NIH, Bethesda, MD 20892-1370, USA.
Traynor
T
T
Pohl
H
H
Thomas
D W
DW
Coffman
T M
TM
Briggs
J P
JP
D000818:Animals; D005246:Feedback; D007678:Kidney Glomerulus / Q000502:physiology*; D007684:Kidney Tubules / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D017482:Receptors, Thromboxane / Q000172:deficiency* / Q000235:genetics; D014517:Ureteral Obstruction / Q000503:physiopathology*; D014661:Vasoconstriction / Q000502:physiology*
D017482:Receptors, Thromboxane