Renal blood flow and pelvic pressure after 4 weeks of total upper urinary tract obstruction in the pig. The effect of a TxA2 synthetase inhibitor on active preglomerular vasoconstriction.

In 8 female pigs complete unilateral ureteral obstruction was investigated over a 4 weeks period. The pigs were monitored with intrapelvic pressure measurements and by 131-I-hippuran scintigraphy twice a week; one group without and one with TxA2 blocking, UK-38,485 [3-(1H-imidazol-1-yl-methyl)-2-methyl-1H-indol-1-propanoic acid], which is a well-known selective thromboxane synthetase inhibitor. During the course of obstruction there was an ipsilateral linear reduction of split function to background level and a net reduction in total hippuran clearance in both groups. On the obstructed side there was a linear reduction of hippuran clearance from 116 +/- 26 ml/min to 11 +/- 3 ml/min during the first 2 weeks of obstruction. The TxA2 synthetase inhibitor, 5 mg/kg reduced se-TxB2 to almost zero for at least one hour after i.v. administration. One week after obstruction the pelvic pressure was 45 +/- 5 cm H2O) administration of the TxA2 synthetase inhibitor. The pelvic pressure remained elevated throughout the period of observation. The study confirmed earlier work which showed that total ureteral obstruction caused complete cessation of kidney function within a few weeks, but contradicts previous studies because there was no increase in renal blood flow after thromboxane blockade. These differences may be explained by several mechanisms. The continuing increase in pelvic pressure suggested that it was not only a preglomerular vasoconstriction which was responsible for the renal flow reduction, but that there was also a postglomerular vasoconstriction.