enalaprilat-anhydrous and ozagrel

After uninephrectomy in the young rat, renal blood flow (RBF) increases at normal renal perfusion pressure (RPP) but not at reduced RPP. To evaluate the role of endogenous prostaglandins on these effects, RBF was measured during reduction in RPP in rats that were uninephrectomized within 1 wk of age and studied at 33-41 days of age. After acute cyclooxygenase inhibition, autoregulation improved; RBF was unchanged at normal RPP but increased at lower pressures with concomitant decrease in renal venous plasma renin activity (PRA). Prostaglandin inhibition also improved autoregulatory efficiency in acutely uninephrectomized and sham-operated young rats. Infusion of a thromboxane synthesis inhibitor had no effect on the pressure-flow relationship or on PRA, whereas angiotensin converting enzyme inhibition increased RBF at all measured RPP without affecting autoregulation. We conclude that increased RBF at normal RPP in the uninephrectomized young rat is not maintained by increased prostaglandin synthesis or decreased thromboxane- or angiotensin-dependent vasoconstriction. However, by maintaining increased vasoconstriction at reduced RPP, prostaglandin-dependent renin release reduces autoregulatory efficiency in the young rat.

Topics: Animals; Blood Pressure; Enalapril; Enalaprilat; Female; Homeostasis; Indomethacin; Male; Meclofenamic Acid; Methacrylates; Nephrectomy; Prostaglandins; Rats; Renal Circulation; Renin; Vascular Resistance; Vasodilation

To evaluate the relative contribution of endogenous vasoactive compounds to maintenance of increased renal vascular resistance in neonatal obstructive nephropathy, cardiac output and renal blood flow were measured using radioactive microspheres in 25 +/- 3 day-old guinea pigs subjected to unilateral partial ureteral constriction within the first two days of life. Mass and renal blood flow of the obstructed kidney were significantly lower than those of the contralateral kidney. Following a control period, thromboxane synthesis was blocked by infusion of OKY-046, after which prostaglandin synthesis was inhibited by indomethacin. In a separate group of animals, angiotensin converting enzyme inhibitor, MK-422, was infused before or after administration of OKY-046. While neither OKY-046 nor indomethacin had a consistent effect on vascular resistance, infusion of MK-422 resulted in selective reduction of renal vascular resistance of the obstructed kidney compared to resistance in the intact kidney and other vascular beds. Removal of the contralateral kidney at the time of ureteral constriction in an additional group of animals resulted in hypertrophy and vasodilation of the obstructed kidney which was not altered by thromboxane or cyclooxygenase inhibition. We conclude that in the neonatal kidney subjected to ipsilateral chronic partial ureteral obstruction, vasoconstriction is mediated at least in part by angiotensin II, but not by thromboxane. Furthermore, vasodilation of the obstructed kidney resulting from contralateral nephrectomy is not dependent on prostaglandin synthesis. Renal vascular resistance of the kidney with prolonged partial ureteral constriction in early development thus appears to be inversely related to renal growth and is not significantly mediated by endogenous prostanoids.

Topics: Angiotensin II; Animals; Animals, Newborn; Cardiac Output; Enalapril; Enalaprilat; Female; Guinea Pigs; Indomethacin; Kidney; Male; Methacrylates; Microspheres; Prostaglandins; Renal Circulation; Strontium Radioisotopes; Thromboxanes; Time Factors; Ureteral Obstruction; Vascular Resistance