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A RE-EVALUATION OF THE ROLE OF THE AUTONOMIC NERVOUS SYSTEM UPON RENAL FUNCTION FROM THE VIEW OF A PHARMACOLOGIST RONALD L. WILLIAMS* The key to the mystery is not to befound in the accumulation ofinstances, but in the intrinsic character ofeach instance.—A. N. Whitehead [i]. Hardly any battery ofnewfacts could havepersuaded a Greek that the universe had an attribute so repugnant to him as infinity; hardly any such battery couldpersuade a modern that it is hierarchical.—C. S. Lewis [2]. G. A. G. Mitchell [3, 4] at the University of Manchester, has shown that the kidney (ofman) receives a profuse and widespread nerve supply. This supply was from both sympathetic and parasympathetic nerves. In spite of this profuse innervation, very little attention has been given to the role ofrenal nerves. The most prevalent opinion, until very recently, has been that the parasympathetic nerves play no important role in renal hemodynamics or salt excretion. The sympathetic innervation was said to have a minor function in producing vasoconstriction during acute circulatory stress. Individual investigators have from time to time proposed a more important role, but their ideas have never been accepted as important enough to influence that general knowledge which recurs in textbooks and reviews of electrolytes and renal function. I believe that this long lack of belief in any real importance of the renal nerves has inhibited research in this area which may have broad implications for the interpretations of the way in which the body regulates its electrolyte balance through renal function. This subject is an important link in the relation ofthe central nervous system to water and electrolyte metabolism. It is the oldest and most controversial area in renal physiology. There is an excellent review of * Department ofPharmacology, Louisiana State University, School ofMedicine, New Orleans. 25I the general subject byJoseph Cort [5]. I shall attempt to limit this polemical investigation to the actions ofthe peripheral autonomic nervous system, and drugs which mimic the action of nervous stimulation, on renal salt excretion. For a time, it was rather generally supposed that the rate ofproduction of mineralocorticoids such as DOCA and aldosterone would be shown to be the way in which the body controls sodium homeostasis through renal function. Notwithstanding the fact that the mineralocorticoids are necessary for electrolyte balance, the direct renal effect of aldosterone is equivocal and slow in onset [6, 7]. It is now known that saline loading in the dog increases sodium excretion even in the presence of decreased glomerular filtration (GFR); this increased sodium excretion is independent of mineralocorticoid, vasopressin, dilution of plasma proteins, or angiotensin [8, 9]. Still unanswered is the nature of renal escape from the sodium-retaining action of aldosterone. The escape is not related to changes in blood pressure, GFR, extracellular fluid volume, or plasma volume, but to some unknown factor which increases tubular rejection of sodium [10]. Renal nerves are usually ignored in the discussion, or their role is not critically examined. Remembering that the kidneys are profusely innervated, this lack of information as to the function of these nerves becomes intriguing. The question is simply: What are all those nerves doing there? Only for a minor role in hemodynamic adjustment, is the usual refrain. However, the question becomes louder when considering the recent evidence of the direct renal effects during intrarenal infusion ofneurotransmitters and autonomic drugs. It was not until 1963 that acetylcholine, the chemical transmitter of cholinergic nerves, was known to produce saluresis and diuresis through a direct renal action [11]. This direct renal effect of acetylcholine was recently documented by several workers. We have shown that cholinergic drugs produce saluresis by increasing the tubular rejection of sodium [12]. A. C. Barger and his associates [13] have shown that norepinephrine, the neurotransmitter from adrenergic sympathetic nerves, invariably produced sodium retention in the infused kidney in unanesthetized dogs, although the hemodynamic changes were variable. Homer Smith [14] stated in 1957 that "no physiologic circumstance is known which leads to unequivocal natriuresis except the administration 252 Ronald L. Williams · Nervous System and Renal Function Perspectives in Biology and Medicine · Winter 1967 ofsodium chloride, and even here the magnitude ofnatriuresis although highly variable, is frequently not very remarkable." Perhaps the...

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