Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1996 Jul 9;93(14):7397–7404. doi: 10.1073/pnas.93.14.7397

Hypothalamic integration of body fluid regulation.

D A Denton 1, M J McKinley 1, R S Weisinger 1
PMCID: PMC38996  PMID: 8693005

Abstract

The progression of animal life from the paleozoic ocean to rivers and diverse econiches on the planet's surface, as well as the subsequent reinvasion of the ocean, involved many different stresses on ionic pattern, osmotic pressure, and volume of the extracellular fluid bathing body cells. The relatively constant ionic pattern of vertebrates reflects a genetic "set" of many regulatory mechanisms--particularly renal regulation. Renal regulation of ionic pattern when loss of fluid from the body is disproportionate relative to the extracellular fluid composition (e.g., gastric juice with vomiting and pancreatic secretion with diarrhea) makes manifest that a mechanism to produce a biologically relatively inactive extracellular anion HCO3- exists, whereas no comparable mechanism to produce a biologically inactive cation has evolved. Life in the ocean, which has three times the sodium concentration of extracellular fluid, involves quite different osmoregulatory stress to that in freshwater. Terrestrial life involves risk of desiccation and, in large areas of the planet, salt deficiency. Mechanisms integrated in the hypothalamus (the evolutionary ancient midbrain) control water retention and facilitate excretion of sodium, and also control the secretion of renin by the kidney. Over and above the multifactorial processes of excretion, hypothalamic sensors reacting to sodium concentration, as well as circumventricular organs sensors reacting to osmotic pressure and angiotensin II, subserve genesis of sodium hunger and thirst. These behaviors spectacularly augment the adaptive capacities of animals. Instinct (genotypic memory) and learning (phenotypic memory) are melded to give specific behavior apt to the metabolic status of the animal. The sensations, compelling emotions, and intentions generated by these vegetative systems focus the issue of the phylogenetic emergence of consciousness and whether primal awareness initially came from the interoreceptors and vegetative systems rather than the distance receptors.

Full text

PDF
7397

Images in this article

7399Fig. 1
on p.7399
7401Fig. 2
on p.7401
7403Fig. 3
on p.7403

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ANDERSSON B. The effect of injections of hypertonic NaCl-solutions into different parts of the hypothalamus of goats. Acta Physiol Scand. 1953;28(2-3):188–201. doi: 10.1111/j.1748-1716.1953.tb00969.x. [DOI] [PubMed] [Google Scholar]
  2. Andersson B., Leksell L. G., Lishajko F. Perturbations in fluid balance induced by medially placed forebrain lesions. Brain Res. 1975 Dec 5;99(2):261–275. doi: 10.1016/0006-8993(75)90028-1. [DOI] [PubMed] [Google Scholar]
  3. Andersson B., Olsson K. On central control of body fluid homeostasis. Cond Reflex. 1973 Jul-Sep;8(3):147–159. doi: 10.1007/BF03000495. [DOI] [PubMed] [Google Scholar]
  4. Bealer S. L., Johnson A. K. Sodium consumption following lesions surrounding the anteroventral third ventricle. Brain Res Bull. 1979 Mar-Apr;4(2):287–290. doi: 10.1016/0361-9230(79)90294-6. [DOI] [PubMed] [Google Scholar]
  5. Blair-West J. R., Burns P., Denton D. A., Ferraro T., McBurnie M. I., Tarjan E., Weisinger R. S. Thirst induced by increasing brain sodium concentration is mediated by brain angiotensin. Brain Res. 1994 Feb 21;637(1-2):335–338. doi: 10.1016/0006-8993(94)91256-4. [DOI] [PubMed] [Google Scholar]
  6. Blair-West J. R., Coghlan J. P., Denton D. A., Nelson J. F., Orchard E., Scoggins B. A., Wright R. D., Myers K., Junqueira C. L. Physiological, morphological and behavioural adaptation to a sodium deficient environment by wild native Australian and introduced species of animals. Nature. 1968 Mar 9;217(5132):922–928. doi: 10.1038/217922a0. [DOI] [PubMed] [Google Scholar]
  7. Blair-West J. R., Denton D. A., Gellatly D. R., McKinley M. J., Nelson J. F., Weisinger R. S. Changes in sodium appetite in cattle induced by changes in CSF sodium concentration and osmolality. Physiol Behav. 1987;39(4):465–469. doi: 10.1016/0031-9384(87)90374-x. [DOI] [PubMed] [Google Scholar]
  8. Blair-West J. R., Denton D. A., McKinley M. J., Weisinger R. S. Angiotensin-related sodium appetite and thirst in cattle. Am J Physiol. 1988 Aug;255(2 Pt 2):R205–R211. doi: 10.1152/ajpregu.1988.255.2.R205. [DOI] [PubMed] [Google Scholar]
  9. Blair-West J. R., Denton D. A., Nelson J. F., McKinley M. J., Radden B. G., Ramshaw E. H. Recent studies of bone appetite in cattle. Acta Physiol Scand Suppl. 1989;583:53–58. [PubMed] [Google Scholar]
  10. Buggy J., Jonhson A. K. Preoptic-hypothalamic periventricular lesions: thirst deficits and hypernatremia. Am J Physiol. 1977 Jul;233(1):R44–R52. doi: 10.1152/ajpregu.1977.233.1.R44. [DOI] [PubMed] [Google Scholar]
  11. Bunnemann B., Fuxe K., Ganten D. The brain renin-angiotensin system: localization and general significance. J Cardiovasc Pharmacol. 1992;19 (Suppl 6):S51–S62. doi: 10.1097/00005344-199219006-00010. [DOI] [PubMed] [Google Scholar]
  12. DENTON D. A. EVOLUTIONARY ASPECTS OF THE EMERGENCE OF ALDOSTERONE SECRETION AND SALT APPETITE. Physiol Rev. 1965 Apr;45:245–295. doi: 10.1152/physrev.1965.45.2.245. [DOI] [PubMed] [Google Scholar]
  13. DENTON D. A., SABINE J. R. The selective appetite for Na ions shown by Na ion-deficient sheep. J Physiol. 1961 Jun;157:97–116. doi: 10.1113/jphysiol.1961.sp006708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. DENTON D. A. The study of sheep with permanent unilateral parotid fistulae. Q J Exp Physiol Cogn Med Sci. 1957 Jan;42(1):72–95. doi: 10.1113/expphysiol.1957.sp001244. [DOI] [PubMed] [Google Scholar]
  15. DENTON D. A., WYNN V., McDONALD I. R., SIMON S. Renal regulation of the extracellular fluid. II: Renal physiology in electrolyte subtraction. Acta Med Scand Suppl. 1951;261:1–202. [PubMed] [Google Scholar]
  16. Denton D. A., Blair-West J. R., McBurnie M., Weisinger R. S., Logan A., Gonzales A. M., Baird A. Central action of basic fibroblast growth factor on ingestive behaviour in mice. Physiol Behav. 1995 Apr;57(4):747–752. doi: 10.1016/0031-9384(94)00319-x. [DOI] [PubMed] [Google Scholar]
  17. Fitts D. A., Tjepkes D. S., Bright R. O. Salt appetite and lesions of the ventral part of the ventral median preoptic nucleus. Behav Neurosci. 1990 Oct;104(5):818–827. doi: 10.1037//0735-7044.104.5.818. [DOI] [PubMed] [Google Scholar]
  18. Fitzsimons J. T. Angiotensin stimulation of the central nervous system. Rev Physiol Biochem Pharmacol. 1980;87:117–167. doi: 10.1007/BFb0030897. [DOI] [PubMed] [Google Scholar]
  19. Galun E., Tur-Kaspa I., Assia E., Burstein R., Strauss N., Epstein Y., Popovtzer M. M. Hyponatremia induced by exercise: a 24-hour endurance march study. Miner Electrolyte Metab. 1991;17(5):315–320. [PubMed] [Google Scholar]
  20. Johnson A. K., Zardetto-Smith A. M., Edwards G. L. Integrative mechanisms and the maintenance of cardiovascular and body fluid homeostasis: the central processing of sensory input derived from the circumventricular organs of the lamina terminalis. Prog Brain Res. 1992;91:381–393. doi: 10.1016/s0079-6123(08)62357-2. [DOI] [PubMed] [Google Scholar]
  21. Leksell L. G., Denton D. A., Fei D. T., McKinley M. J., Müller A. F., Weisinger R. S., Young H. On the importance of CSF Na in the regulation of renal sodium excretion and renin release. Acta Physiol Scand. 1982 May;115(1):141–146. doi: 10.1111/j.1748-1716.1982.tb07056.x. [DOI] [PubMed] [Google Scholar]
  22. Mangiapane M. L., Thrasher T. N., Keil L. C., Simpson J. B., Ganong W. F. Deficits in drinking and vasopressin secretion after lesions of the nucleus medianus. Neuroendocrinology. 1983 Jul;37(1):73–77. doi: 10.1159/000123518. [DOI] [PubMed] [Google Scholar]
  23. McKinley M. J., Badoer E., Oldfield B. J. Intravenous angiotensin II induces Fos-immunoreactivity in circumventricular organs of the lamina terminalis. Brain Res. 1992 Oct 30;594(2):295–300. doi: 10.1016/0006-8993(92)91138-5. [DOI] [PubMed] [Google Scholar]
  24. McKinley M. J., Bicknell R. J., Hards D., McAllen R. M., Vivas L., Weisinger R. S., Oldfield B. J. Efferent neural pathways of the lamina terminalis subserving osmoregulation. Prog Brain Res. 1992;91:395–402. doi: 10.1016/s0079-6123(08)62358-4. [DOI] [PubMed] [Google Scholar]
  25. McKinley M. J., Blaine E. H., Denton D. A. Brain osmoreceptors, cerebrospinal fluid electrolyte composition and thirst. Brain Res. 1974 Apr 26;70(3):532–537. doi: 10.1016/0006-8993(74)90264-9. [DOI] [PubMed] [Google Scholar]
  26. McKinley M. J. Common aspects of the cerebral regulation of thirst and renal sodium excretion. Kidney Int Suppl. 1992 Jun;37:S102–S106. [PubMed] [Google Scholar]
  27. McKinley M. J., Congiu M., Denton D. A., Park R. G., Penschow J., Simpson J. B., Tarjan E., Weisinger R. S., Wright R. D. The anterior wall of the third cerebral ventricle and homeostatic responses to dehydration. J Physiol (Paris) 1984;79(6):421–427. [PubMed] [Google Scholar]
  28. McKinley M. J., Denton D. A., Coghlan J. P., Harvey R. B., McDougall J. G., Rundgren M., Scoggins B. A., Weisinger R. S. Cerebral osmoregulation of renal sodium excretion--a response analogous to thirst and vasopressin release. Can J Physiol Pharmacol. 1987 Aug;65(8):1724–1729. doi: 10.1139/y87-271. [DOI] [PubMed] [Google Scholar]
  29. McKinley M. J., Denton D. A., Leksell L. G., Mouw D. R., Scoggins B. A., Smith M. H., Weisinger R. S., Wright R. D. Osmoregulatory thirst in sheep is disrupted by ablation of the anterior wall of the optic recess. Brain Res. 1982 Mar 18;236(1):210–215. doi: 10.1016/0006-8993(82)90048-8. [DOI] [PubMed] [Google Scholar]
  30. McKinley M. J., Denton D. A., Weisinger R. S. Sensors for antidiuresis and thirst--osmoreceptors or CSF sodium detectors? Brain Res. 1978 Feb 3;141(1):89–103. doi: 10.1016/0006-8993(78)90619-4. [DOI] [PubMed] [Google Scholar]
  31. McKinley M. J., Evered M., Mathai M., Coghlan J. P. Effects of central losartan on plasma renin and centrally mediated natriuresis. Kidney Int. 1994 Dec;46(6):1479–1482. doi: 10.1038/ki.1994.424. [DOI] [PubMed] [Google Scholar]
  32. McKinley M. J., Rundgren M., Coghlan J. P. Cerebral osmoregulatory reduction of plasma renin concentration in sheep. Acta Physiol Scand. 1994 Nov;152(3):323–332. doi: 10.1111/j.1748-1716.1994.tb09812.x. [DOI] [PubMed] [Google Scholar]
  33. Mouw D. R., Vander A. J. Evidence for brain Na receptors controlling renal Na excretion and plasma renin activity. Am J Physiol. 1970 Sep;219(3):822–832. doi: 10.1152/ajplegacy.1970.219.3.822. [DOI] [PubMed] [Google Scholar]
  34. Muller A. F., Denton D. A., McKinley M. J., Tarjan E., Weisinger R. S. Lowered cerebrospinal fluid sodium antagonizes effect of raised blood sodium on salt appetite. Am J Physiol. 1983 Jun;244(6):R810–R814. doi: 10.1152/ajpregu.1983.244.6.R810. [DOI] [PubMed] [Google Scholar]
  35. Nicolaïdis S. Early systemic responses to orogastric stimulation in the regulation of food and water balance: functional and electrophysiological data. Ann N Y Acad Sci. 1969 May 15;157(2):1176–1203. doi: 10.1111/j.1749-6632.1969.tb12942.x. [DOI] [PubMed] [Google Scholar]
  36. Park R., Denton D. A., McKinley M. J., Pennington G., Weisinger R. S. Intracerebroventricular saccharide infusions inhibit thirst induced by systemic hypertonicity. Brain Res. 1989 Jul 24;493(1):123–128. doi: 10.1016/0006-8993(89)91006-8. [DOI] [PubMed] [Google Scholar]
  37. Pitts G. C. An evolutionary approach to pain. Perspect Biol Med. 1994 Winter;37(2):275–284. doi: 10.1353/pbm.1994.0085. [DOI] [PubMed] [Google Scholar]
  38. SCHMIDT-NIELSEN K. The salt-secreting gland of marine birds. Circulation. 1960 May;21:955–967. doi: 10.1161/01.cir.21.5.955. [DOI] [PubMed] [Google Scholar]
  39. Sakai R. R., Chow S. Y., Epstein A. N. Peripheral angiotensin II is not the cause of sodium appetite in the rat. Appetite. 1990 Dec;15(3):161–170. doi: 10.1016/0195-6663(90)90017-3. [DOI] [PubMed] [Google Scholar]
  40. Simpson J. B., Routtenberg A. Subfornical organ: site of drinking elicitation by angiotensin II. Science. 1973 Sep 21;181(4105):1172–1175. doi: 10.1126/science.181.4105.1172. [DOI] [PubMed] [Google Scholar]
  41. Tarjan E., Denton D. A., Weisinger R. S. Atrial natriuretic peptide inhibits water and sodium intake in rabbits. Regul Pept. 1988 Oct;23(1):63–75. doi: 10.1016/0167-0115(88)90422-3. [DOI] [PubMed] [Google Scholar]
  42. Tarjan E., Denton D. A., Weisinger R. S. Cerebral sodium sensors in the sodium-deplete sheep. Brain Res. 1989 Oct 23;500(1-2):352–358. doi: 10.1016/0006-8993(89)90331-4. [DOI] [PubMed] [Google Scholar]
  43. Thrasher T. N., Keil L. C., Ramsay D. J. Lesions of the organum vasculosum of the lamina terminalis (OVLT) attenuate osmotically-induced drinking and vasopressin secretion in the dog. Endocrinology. 1982 May;110(5):1837–1839. doi: 10.1210/endo-110-5-1837. [DOI] [PubMed] [Google Scholar]
  44. Thunhorst R. L., Ehrlich K. J., Simpson J. B. Subfornical organ participates in salt appetite. Behav Neurosci. 1990 Aug;104(4):637–642. doi: 10.1037//0735-7044.104.4.637. [DOI] [PubMed] [Google Scholar]
  45. Thunhorst R. L., Fitts D. A. Peripheral angiotensin causes salt appetite in rats. Am J Physiol. 1994 Jul;267(1 Pt 2):R171–R177. doi: 10.1152/ajpregu.1994.267.1.R171. [DOI] [PubMed] [Google Scholar]
  46. Vincent J. D., Arnauld E., Bioulac B. Activity of osmosensitive single cells in the hypothalamus of the behaving monkey during drinking. Brain Res. 1972 Sep 29;44(2):371–384. doi: 10.1016/0006-8993(72)90309-5. [DOI] [PubMed] [Google Scholar]
  47. Vivas L., Chiaraviglio E., Carrer H. F. Rat organum vasculosum laminae terminalis in vitro: responses to changes in sodium concentration. Brain Res. 1990 Jun 11;519(1-2):294–300. doi: 10.1016/0006-8993(90)90091-o. [DOI] [PubMed] [Google Scholar]
  48. WOLF A. V. Osmometric analysis of thirst in man and dog. Am J Physiol. 1950 Apr 1;161(1):75–86. doi: 10.1152/ajplegacy.1950.161.1.75. [DOI] [PubMed] [Google Scholar]
  49. Weisinger R. S., Blair-West J. R., Denton D. A., Tarjan E. Central administration of somatostatin suppresses the stimulated sodium intake of sheep. Brain Res. 1991 Mar 15;543(2):213–218. doi: 10.1016/0006-8993(91)90030-y. [DOI] [PubMed] [Google Scholar]
  50. Weisinger R. S., Considine P., Denton D. A., McKinley M. J. Rapid effect of change in cerebrospinal fluid sodium concentration on salt appetite. Nature. 1979 Aug 9;280(5722):490–491. doi: 10.1038/280490a0. [DOI] [PubMed] [Google Scholar]
  51. Weisinger R. S., Denton D. A., Di Nicolantonio R., Hards D. K., McKinley M. J., Oldfield B., Osborne P. G. Subfornical organ lesion decreases sodium appetite in the sodium-depleted rat. Brain Res. 1990 Aug 27;526(1):23–30. doi: 10.1016/0006-8993(90)90245-7. [DOI] [PubMed] [Google Scholar]
  52. Weisinger R. S., Denton D. A., McKinley M. J., Miselis R. R., Park R. G., Simpson J. B. Forebrain lesions that disrupt water homeostasis do not eliminate the sodium appetite of sodium deficiency in sheep. Brain Res. 1993 Nov 19;628(1-2):166–178. doi: 10.1016/0006-8993(93)90952-j. [DOI] [PubMed] [Google Scholar]
  53. Weisinger R. S., Denton D. A., McKinley M. J., Muller A. F., Tarjan E. Cerebrospinal fluid sodium concentration and salt appetite. Brain Res. 1985 Feb 4;326(1):95–105. doi: 10.1016/0006-8993(85)91388-5. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES