A B S T R A C T Studies were undertaken to characterize the renal responses to acute unilateral renal denervation and the mechanisms involved in these responses. Denervation was produced in anesthetized nondiuretic rats by application of phenol to the left renal artery. Studies were also performed in sham-denervated nondiuretic rats. Whole kidney and individual nephron studies were performed before and after denervation or sham denervation. Denervation increased urine volume from the left kidney to about twice its control value (P < 0.001) and increased urinary sodium excretion from 332 neq min' to 1,887 neq min' (P <0.001). Glomerular filtration rate (GFR) and renal plasma flow (RPF) remained unchanged in both kidneys after the procedure. The innervated right kidney showed no changes in urine volume or in sodium excretion. After denervation, late proximal ratio of tubular fluid inulin concentration to that of plasma [ (F/P) In] decreased from 2.23 to 1.50 (P < 0.001) while single nephron GFR remained unchanged. Absolute reabsorption decreased from 16.5 to 9.9 nl min' (P <0.001). (F/P) i ratios were also decreased in early distal (from 6.21 to 3.18, P <0.001) and late distal convolutions (from 16.41 to 8.33, P < 0.001) during the experimental period. (F/P) Na ratios remained unchanged in the early distal convolutions, but increased from 0.18 to 0.38 (P < 0.01) in late distal convolutions after denervation. Absolute Na reabsorption after denervation increased in the loop of Henle, distal convolution, and collecting ducts. Any changes in intrarenal hydrostatic pressures
The present study demonstrates that repeated administration of SKF-38393, a D1-dopamine agonist, is necessary for maximal behavioral supersensitivity of D1-dopamine receptor responses in neonatal 6-OHDA-lesioned rats, confirming earlier work. This repeated administration of SKF-38393, which is referred to as priming of D1-dopamine receptor responses, resulted in a progressive increase in locomotor activity, as well as several other behaviors. This priming phenomenon lasted at least 6 months. Repeated administration of the D2-dopamine agonist LY-171555 also increased behavioral responses to the D1-dopamine agonist. However, previous administration of a D2-dopamine agonist was not necessary for priming of D1-dopamine receptor responses, because D1-dopamine receptor priming could be produced in the presence of a D2-dopamine receptor antagonist. Blockade of D1-dopamine receptors with SCH-23390 prior to injection of SKF-38393 prevented the increasing responsiveness following repeated administration of this D1-dopamine agonist. Selective neonatal destruction of dopamine-containing neurons produced the same result as did destruction of catecholamine-containing neurons, indicating that the noradrenergic system is not involved in this phenomenon. Priming of D1-dopamine receptor responses by repeated administration of SKF-38393 was not observed in unlesioned controls or in rats that received catecholamine-depleting lesions as adults. Repeated administration of scopolamine also was able to prime behavioral responses to SKF-38393 in neonatal 6-OHDA-lesioned rats, indicating that endogenous release of dopamine can prime D1-dopamine receptor responses in neonatally lesioned rats. In addition, responses to indirect-acting agonists were enhanced in rats that had been primed with a D1-dopamine agonist when compared wit responses in unprimed animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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