Carl W. Gottschalk**, Romulo E. Colindres, Nicholas G. Moss, Paula R. Rogenes and Laszlo Szalay***,     Departments of Medicine and Physiology University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA

Publisher Summary

This chapter discusses that efferent renal nerve stimulation affect both proximal tubular transport of salt and water and the resistance of the renal vessels. It highlights the possibility of a neural mechanism, a renorenal reflex, being responsible for the coordination of the excretory activity of the two kidneys that occurs when the function of one of the kidneys is altered. The condition under which the mechanism becomes operative requires further identification, but it is not restricted to the anesthetized state. Renal chemoreceptors and the mechanoreceptors provide an afferent mechanism for ipsilateral and contralateral renorenal reflexes integrated at the spinal cord level. This appears to be the operative mechanism in at least one instance of coordination of renal excretory activity. The full extent of the neural mechanism, involving different neurotransmitters with opposing effects, almost certainly exceeds in complexity of the simple system.

MICROPUNCTURE AND CLEARANCE EXPERIMENTS

Although a proximal tubular effect was first reported by Bencsath et al. (1972), the Chapel Hill group was the first to provide extensive micropuncture documentation for such a result. Bello-Reuss et al. (1975) characterized the renal response to acute unilateral denervation in an extensive study of sham denervated and denervated kidneys. Denervation of a kidney was accomplished by stripping the renal artery of its adventitia and coating it with a solution of 10% phenol in alcohol. For a variety of reasons the functional changes observed cannot be attributed to a direct effect of phenol on kidney function: no norepinephrine could be detected in the kidneys several days after denervation; incomplete denervation from splanchnic nerve crushing produced similar, but quantitatively smaller results than the apparently complete chemical denervation, and these effects were reversed by electrical stimulation of the distal end of the cut splanchnic nerve. Coating the artery with lidocaine instead of phenol produced similar but transitory effects.

No changes were observed in any function of either kidney of sham-denervated rats. Following unilateral denervation in hydropenic animals urine volume from the denervated kidney increased to about twice its control value, and urinary sodium excretion increased sixfold. There was no change in urine volume or sodium excretion from the innervated kidney. Glomerular filtration rate (GFR) and renal plasma flow (RPF) remained unchanged in both kidneys after the procedure. SNGFR remained unchanged after denervation. The fluid-to-plasma ratio of inulin decreased in samples of fluid collected from late proximal tubules of denervated kidneys indicating a 60% decrease in water and sodium reabsorption by the proximal tubule. Absolute water and sodium reabsorption increased in the loop of Henle, distal convolution, and collecting ducts, but not enough to compensate for the 60% decrease in the proximal tubule.

Denervation caused no change in estimated glomerular capillary or efferent arteriolar pressure. There were very small increases in hydrostatic pressure in proximal and distal convolutions and in small peritubular capillaries. Since there was no change in whole kidney or single nephron GFR and renal plasma flow was unchanged, it is unlikely that there was a change in overall or superficial nephron colloid osmotic pressure or significant redistribution of renal blood flow. It thus appears that the physical factors did not play an important role in the observed changes in tubular reabsorption.

Similar results were observed in animals expanded 10% above their body weight by an infusion of isotonic saline solution (Bello-Reuss et al. 1977). There was no change in GFR or RPF in either kidney after unilateral denervation or sham denervation. Urine flow and sodium excretion by denervated kidneys was doubled. Simultaneously urine flow and sodium excretion by the contralateral innervated kidneys fell by half so that there was little change in total salt and water excretion. I will return to this striking finding shortly. After denervation SNGFR remained unchanged. The F/P inulin ratio in fluid from late proximal tubules decreased, indicating a fall in water and sodium reabsorption in the proximal tubule of more than 50%. Absolute water and sodium reabsorption increased after denervation in the loop of Henle, distal convolution and collecting ducts but not enough to prevent the natriuresis and diuresis.

In another series of experiments in anesthetized rats the natriuresis and diuresis resulting from unilateral crushing of the greater splanchnic nerve was reversed by electrical stimulation of the distal portion of the cut nerve with square wave pulses of 0.5 msec duration, voltage twice threshold, and 1 or 2 Hz frequency (Bello-Reuss et al. 1976). Kidney GFR and RPF and SNGFR remained unchanged during stimulation. Nerve stimulation produced a reduction of approximately 25% in urine flow and sodium excretion due to increased water reabsorption in the proximal tubule. In 5 of 6 animals, stimulation at 1 Hz was followed by an increase in proximal F/P inulin ratio. In the one animal in which there was no change in F/P inulin there was no change in sodium excretion by the kidney. For unknown reasons, the appropriate fibers apparently were not stimulated in that animal. On cessation of stimulation the F/P inulin ratio returned to control values. Subsequent stimulation at 2 Hz caused an increase in F/P inulin ratio in all animals. Recordings of the compound action potential of the stimulated nerves indicated that the effect on tubular reabsorption resulted from stimulation of slowly conducting C fibers.

Recent studies both in Budapest (Bencsath et al. 1979) and in Chapel Hill (Colindres et al. 1980) demonstrate that the denervation effect is not a transient one that is observed only...