Cerebral osmoregulation of renal sodium excretion-a response analogous to thirst and vasopressin release' MICHAEL J. MCKINLEY,~ DEREK A. DENTQN, JOHN P. COGHLAN, RQDNEY B. HARVEY, JOHN G. MCDOUGALL, MATS RUNDGREN,~ BRUCE A. SCQGINS, AND RICHARD S. WEISINGER Howard %;korey Institute of Experimental Physiokogy and LU~dkcine, University ~j.~We&bokcrsae, ParkvSkle 3052, AustruEia Received July 38, 1 986 MCKINLEY, M. J., DENTON, D. A., COGHLAN, J. P., HARVEY, R. B., MCDQUGAI,I,, J. G., RUNDGREN, M., SCQGGINS, B. A., and WEISINGER, R. S. 1987. Cerebral osmoregulation of renal sodium excretion-a response analogous to thirst and vasopressin release. Can. J. Physiol. Phm~acol. 65: 1724- 1729. Studies in sheep have shown that renal excretion of sodium may be under osmoregulatory control. When sheep become dehydrated, or are infused intravenously with hypertonic saline, they increase renal Na excretion in addition to secreting vasopressin and developing a thirst. These natriuretic, antidiuretic, and dipsogenic responses to dehydration and hypertonicity can be greatly reduced by lowering the cerebrospinal fluid NaCl concentration or by prior ablation of tissue in the anterior wall of the third ventricle. Lowering of cerebrospinal fluid NaCl concentration also prevents postprandial natriuresis which normally occurs in association with a postprandial increase in plasma Na concentration and tonicity. We propose that there is a cerebral osmoregulatory control of Na excretion which may interact with volume influences from the cardiovascular system to mgulate renal Na output. The effector mechanism from brain to kidney mediating such cerebral control of Na excretion is probably homond . MCKINLEY, M. J., DENTON, D. A., CBGHLAN, J. P., HARVEY, R. B., MCDOUGALL, J. G., RUNWREN, M., SCOGGHNS, B. A., et WEHSINGER, R. S. 1987. Cerebral osmoregulation of renal sodium excretion-a response analogous to thirst and vasopressin release. Can. J. Phy siol. P h m a c o l . 65 : 1724- 1 729. Bes Ctudes chez des brebis ont montr6 que 17excrCtion rCnale de sodium pouvait &tre sous contr6le osmorCgulateur.Lorsque les brebis deviennent dCshydratCes, ou qu'elles repivent un perfusion intraveineuse d'une solution saline hypertonique. leur excrktion Na r6nde augmente, eHes sCcrktent de la vasopressine et dCveloppent la soif. Ces rCponses natriurCtiques, antidiurdti- ques et diposgknes A la dkshydration et h I'hypertonicitC peuvent etre nettement rCduites en abaissant la concentration de NaC1 du liquide cephalo-rachidien ou en prClevant auparavant le tissu dans la paroi anttrieure du troisikme ventricule. L'abaissement de la concentration de NaCl du liquide cCphalo-rachidien pr6vient aussi la natriur5se post-prandials qui survient normdement en association avec I'augmentation post-prandiale de Ba concentration de NaCl plasmatique et de la tonicitt. Nous suggerons gu'un eontr6le osmorCgulateur cCrCbral d'excrktion de Na pourrait interagir avec les influences volumiques du systeme cardiovascu- laire pour rkgulariser le dCbit de Na rCnal. Le mCcanisme effecteur du cerveau au rein mCdimt un tel contrale cerkbral d9excrCtion de Na est probablement hormonal. I Traduit par la revue] Introduction T h h t and vasopressin (AMP) secretion in response to in- creases in tonicity of the extracellular fluid are the classical osmoregulatory responses initiated by the cerebral osmorecep- tors (Memey 1947; Wolf 1950). However, these responses, while tending to minimize the disturbance to the composition of body fluids, may not be sufficient to restore the normal ntidieu inte'rieur. For instance, if hypertonicity results from increased intake of a solute such as NaC1, excretion of the excess solute will be necessary before the initial state can be restored, regard- less of whether water is imbibed or there is reduced urine output. When hypertonicity results from dehydration, there is evidence that increased renal excretion of sodium also occurs in this situation (Luke 1973; McKinley et al. 1983b) and it could be argued that this is an appropriate response. For instance, in dehydrated animals, the disturbance to the body fluids can only be corrected if water is available to be imbibed. If water con- tinues to be unavailable, antidiuresis resulting from increased AVP secretion will tend to minimize further dehydration, but does not correct the situation. Natriuresis in response to de- hydration, however, could ameliorate to some extent the hyper- tonicity until water once again becomes available. %is paper was presented at the Hypertension Symposium (Whis- tler, B.C., July 19-21, 1986)' a Satellite Symposium of the 38th HUPS Congress, and has undergone the Journal's usual peer review. '~uthor to whom correspondence may be addressed. 'present address: Department of Physiology, Karolinska Institute, Stockholm, Sweden. In this paper, we wish to present a number of lines of evidence in favour of the proposal that renal excretion of sodium may be another osmoregulatory mechanism under cerebral control. We propose that this control is analogous to the cerebral regulation of osmotically stimulated thirst and AMP release, and evidence to this end from experiments involving brain lesions or man- ipulation of the cerebrospinal fluid QCSF) composition in sheep is reviewed in the following paragraphs. Natriuresis as a response to dehydration In addition to increased thirst and vasopressin secretion, dehydration has been observed to increase the renal excretion of sodium in such diverse mammalian species as rats, mice, rab- bits, dogs, cattle, sheep, and humans (Wiley and Wiley 1933: Bianca et al. 1965; Luke 1973; McKenna and Haines 198 1 ; Zucker et al. 198 1; McKinley et al. 1983b; Thrasher et al. 1984; Memill et al. 1986). This occurs with the onset of dehydration despite the fact that reduction of eztracellular fluid volume, which would tend to be an antinatriuretic influence, is a con- sequence of dehydration. In sheep, dehydration natriuresis may occur up to 48 h after depriving animals of water (Fig. 1). Although renal Na output then falls with more prolonged water deprivation in the sheep (McKinley et al. 1983c), it could be argued that with more prolonged dehydration, even moderate renal excretion of sodium in the face of considerable loss sf extracellular fluid requires some ~natriureticinfluence to be operative to counteract the antinatriuretic influences of the hypovolemia. Ethical considerations prevent the investigation Can. J. Physiol. Pharmacol. Downloaded from www.nrcresearchpress.com by NANJING UNIVERSITY OF SCIENCE AND TECHNOLOGY on 06/07/13 For personal use only.