Alterations in glomerular dynamics in congenital unilateral hydronephrosis
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Description
Hydronephrosis can be defined most easily as an accumulation of fluid in the renal pelvicalyceal system and often is accompanied by a significant reduction in glomerular filtration rate (GFR). In rats with congenital unilateral (right sided) hydronephrosis, treatment with either the angiotensin II receptor antagonist saralasin or the thromboxane A$\sb2$ receptor antagonist SQ-29,548 returns GFR to normal levels. The current study defines the single nephron hemodynamic defect in congenital hydronephrosis and evaluates the roles of angiotensin II (Ang II) and thromboxane A$\sb2$ (TxA$\sb2)$ in this glomerular derangement. Renal micro- puncture studies were performed on animals with a right hydronephrotic kidney (HYDRO, n = 8), non-affected litter mates (CONTROL, n = 6), and four groups of hydronephrotic animals treated with the following antagonists; the TxA$\sb2$ receptor antagonist SQ-29,548 (SQ, n = 7) either one of two Ang II receptor antagonists, saralasin (SAR, n = 7) or DuP-753 (DUP, n = 7), and combined treatment with DuP-753 and SQ-29,548 (S&D, n = 7). SNGFR was significantly reduced in the hydronephrotic kidney compared to control (17.6 $\pm$ 2.0 vs. 35.9 $\pm$ 3.7 nl/min, respectively). Treatment with SQ-29,548 completely restored single nephron function (29.0 $\pm$ 3.0 nl/min), while saralasin and DuP-753 only partially restored function (25.6 $\pm$ 1.6 and 27.8 $\pm$ 1.4 nl/min respectively). Combined SQ-29,548 and DuP-753 treatment resulted in a full recovery of single nephron function to 32.9 $\pm$ 4.4 nl/min. The glomerular ultrafiltration coefficient (K$\sb{\rm f})$ was reduced approximately 45% when comparing CONTROL (2.84 $\pm$.22 nl/min/mmHg) to HYDRO (1.64 $\pm$.08 nl/min/mmHg). K$\sb{\rm f}$ returned to control in SAR, DUP and SQ, and increased above control in S&D (5.58 $\pm$ 1.6 nl/min/mmHg). There were no differences in $\rm P\sb{GC},\ P\sb{T},\ or\ \bar\pi\sb{GC}$ between any of the groups studied. These data indicate that the reduction in SNGFR in congenital hydronephrosis is precipitated by a fall in K$\sb{\rm f}$ which is mediated by both Ang II and TxA$\sb2.$ The observation of an increase in K$\sb{\rm f}$ above CONTROL with combined SQ-29,548 and DuP-753 treatment suggests that Ang II and TxA$\sb2$ alter the ultrafiltration coefficient via separate mechanisms