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. 1984 Dec;74(6):2065–2073. doi: 10.1172/JCI111630

Baroreflex impairment precedes hypertension during chronic cerebroventricular infusion of hypertonic sodium chloride in rats.

R D Buñag, E Miyajima
PMCID: PMC425396  PMID: 6511915

Abstract

Osmotic minipumps were implanted chronically for continuous 11-d infusion of hypertonic sodium chloride (NaCl) into the third cerebral ventricle (ICV) of awake rats to determine whether baroreflex sensitivity would be altered. Systolic and mean pressures, recorded from aortic catheters on day 11 while the rats were anesthetized with alpha-chloralose, were significantly higher in rats infused with artificial cerebrospinal fluid (CSF) containing hypertonic NaCl than in controls similarly infused with artificial CSF alone. Reflex changes in heart rate produced by subsequent intravenous infusions of either phenylephrine or sodium nitroprusside were inhibited, but reflex changes in renal nerve activity were unaltered. Magnitude of reflex bradycardia during pressor responses to phenylephrine, as well as of reflex tachycardia during depressor responses to sodium nitroprusside, was consistently smaller in NaCl-infused than in control rats. By contrast, group differences in attendant renal nerve firing were not significant. After sinoaortic denervation, drug-induced blood pressure effects persisted, but reflex responses in heart rate and renal nerve firing were abolished or markedly diminished. Peripheral effects produced by hypertonic NaCl leakage from the infusion site were considered unlikely because after 11 d of ICV infusion, sodium concentration, though appreciably elevated in CSF samples collected from the cisterna magna, was unaffected in corresponding serum samples. When cardiovascular responses to phenylephrine were recorded while chronic ICV infusions were in progress, awake rats receiving hypertonic NaCl were still normotensive on day 2 yet reflex bradycardia was already attenuated. In showing that baroreflex impairment preceded the development of hypertension, our results suggest that by depressing the anterior hypothalamus, chronic ICV infusion of hypertonic NaCl reduces sympatho-inhibition, and the ensuing baroreflex impairment then elevates blood pressure. However, other mechanisms could also be involved.

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Selected References

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  1. Angell-James J. E., George M. J., Peters C. J. Baroreflex sensitivity in rabbits during the development of experimental renal hypertension and medial sclerosis. Clin Exp Hypertens. 1980 Feb;2(2):321–340. doi: 10.3109/10641968009046427. [DOI] [PubMed] [Google Scholar]
  2. Bristow J. D., Honour A. J., Pickering G. W., Sleight P., Smyth H. S. Diminished baroreflex sensitivity in high blood pressure. Circulation. 1969 Jan;39(1):48–54. doi: 10.1161/01.cir.39.1.48. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Buñag R. D., Butterfield J., Sasaki S. Hypothalamic pressor responses and salt-induced hypertension in Dahl rats. Hypertension. 1983 Jul-Aug;5(4):460–467. doi: 10.1161/01.hyp.5.4.460. [DOI] [PubMed] [Google Scholar]
  5. Calaresu F. R., Ciriello J. Projections to the hypothalamus from buffer nerves and nucleus tractus solitarius in the cat. Am J Physiol. 1980 Jul;239(1):R130–R136. doi: 10.1152/ajpregu.1980.239.1.R130. [DOI] [PubMed] [Google Scholar]
  6. Campese V. M., Romoff M. S., Levitan D., Saglikes Y., Friedler R. M., Massry S. G. Abnormal relationship between sodium intake and sympathetic nervous system activity in salt-sensitive patients with essential hypertension. Kidney Int. 1982 Feb;21(2):371–378. doi: 10.1038/ki.1982.32. [DOI] [PubMed] [Google Scholar]
  7. Ciriello J., Calaresu F. R. Descending hypothalamic pathways with cardiovascular function in the cat: a silver impregnation study. Exp Neurol. 1977 Nov;57(2):561–580. doi: 10.1016/0014-4886(77)90089-9. [DOI] [PubMed] [Google Scholar]
  8. Coleman T. G. Arterial baroreflex control of heart rate in the conscious rat. Am J Physiol. 1980 Apr;238(4):H515–H520. doi: 10.1152/ajpheart.1980.238.4.H515. [DOI] [PubMed] [Google Scholar]
  9. Cowley A. W., Jr, Merrill D., Osborn J., Barber B. J. Influence of vasopressin and angiotensin on baroreflexes in the dog. Circ Res. 1984 Feb;54(2):163–172. doi: 10.1161/01.res.54.2.163. [DOI] [PubMed] [Google Scholar]
  10. Cserr H. Potassium exchange between cerebrospinal fluid, plasma, and brain. Am J Physiol. 1965 Dec;209(6):1219–1226. doi: 10.1152/ajplegacy.1965.209.6.1219. [DOI] [PubMed] [Google Scholar]
  11. Falcon J. C., 2nd, Phillips M. I., Hoffman W. E., Brody M. J. Effects of intraventricular angiotensin II mediated by the sympathetic nervous system. Am J Physiol. 1978 Oct;235(4):H392–H399. doi: 10.1152/ajpheart.1978.235.4.H392. [DOI] [PubMed] [Google Scholar]
  12. Fujita T., Henry W. L., Bartter F. C., Lake C. R., Delea C. S. Factors influencing blood pressure in salt-sensitive patients with hypertension. Am J Med. 1980 Sep;69(3):334–344. doi: 10.1016/0002-9343(80)90002-9. [DOI] [PubMed] [Google Scholar]
  13. Gonzalez E. R., Krieger A. J., Sapru H. N. Central resetting of baroreflex in the spontaneously hypertensive rat. Hypertension. 1983 May-Jun;5(3):346–352. doi: 10.1161/01.hyp.5.3.346. [DOI] [PubMed] [Google Scholar]
  14. Goto A., Ganguli M., Tobian L., Johnson M. A., Iwai J. Effect of an anteroventral third ventricle lesion on NaCl hypertension in Dahl salt-sensitive rats. Am J Physiol. 1982 Oct;243(4):H614–H618. doi: 10.1152/ajpheart.1982.243.4.H614. [DOI] [PubMed] [Google Scholar]
  15. Goto A., Ikeda T., Tobian L., Iwai J., Johnson M. A. Brain lesions in the paraventricular nuclei and catecholaminergic neurons minimize salt hypertension in Dahl salt-sensitive rats. Clin Sci (Lond) 1981 Dec;61 (Suppl 7):53s–55s. doi: 10.1042/cs061053s. [DOI] [PubMed] [Google Scholar]
  16. Guo G. B., Thames M. D., Abboud F. M. Arterial baroreflexes in renal hypertensive rabbits. Selectivity and redundancy of baroreceptor influence on heart rate, vascular resistance, and lumbar sympathetic nerve activity. Circ Res. 1983 Aug;53(2):223–234. doi: 10.1161/01.res.53.2.223. [DOI] [PubMed] [Google Scholar]
  17. Hilton S. M., Spyer K. M. Participation of the anterior hypothalamus in the baroreceptor reflex. J Physiol. 1971 Oct;218(2):271–293. doi: 10.1113/jphysiol.1971.sp009617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ikeda T., Tobian L., Iwai J., Goossens P. Central nervous system pressor responses in rats susceptible and resistant to sodium chloride hypertension. Clin Sci Mol Med Suppl. 1978 Dec;4:225s–227s. doi: 10.1042/cs055225s. [DOI] [PubMed] [Google Scholar]
  19. KRIEGER E. M. NEUROGENIC HYPERTENSION IN THE RAT. Circ Res. 1964 Dec;15:511–521. doi: 10.1161/01.res.15.6.511. [DOI] [PubMed] [Google Scholar]
  20. Korner P. I., West M. J., Shaw J., Uther J. B. "Steady-state" properties of the baroreceptor-heart rate reflex in essential hypertension in man. Clin Exp Pharmacol Physiol. 1974 Jan-Feb;1(1):65–76. doi: 10.1111/j.1440-1681.1974.tb00528.x. [DOI] [PubMed] [Google Scholar]
  21. Krieger E. M. Time course of baroreceptor resetting in acute hypertension. Am J Physiol. 1970 Feb;218(2):486–490. doi: 10.1152/ajplegacy.1970.218.2.486. [DOI] [PubMed] [Google Scholar]
  22. MCCUBBIN J. W., GREEN J. H., PAGE I. H. Baroceptor function in chronic renal hypertension. Circ Res. 1956 Mar;4(2):205–210. doi: 10.1161/01.res.4.2.205. [DOI] [PubMed] [Google Scholar]
  23. Mandelbrod I., Feldman S., Werman R. Mediobasal hypothalamic neurons are excited by the iontophoretic application of sodium. Brain Res. 1983 Aug 22;273(1):35–44. doi: 10.1016/0006-8993(83)91091-0. [DOI] [PubMed] [Google Scholar]
  24. Miyajima E., Buñag R. D. Chronic cerebroventricular infusion of hypertonic sodium chloride in rats reduces hypothalamic sympatho-inhibition and elevates blood pressure. Circ Res. 1984 May;54(5):566–575. doi: 10.1161/01.res.54.5.566. [DOI] [PubMed] [Google Scholar]
  25. Morris M., Campbell W. B., Pettinger W. A. Renin and hemodynamic changes via central adrenergic, cholinergic, and sodium receptor mechanisms in conscious rats. Proc Soc Exp Biol Med. 1976 Jan;151(1):101–104. doi: 10.3181/00379727-151-39152. [DOI] [PubMed] [Google Scholar]
  26. Morrison S. F., Whitehorn D. Baroreceptor reflex gain is not diminished in spontaneous hypertension. Am J Physiol. 1982 Nov;243(5):R500–R505. doi: 10.1152/ajpregu.1982.243.5.R500. [DOI] [PubMed] [Google Scholar]
  27. Nakamura K., Gerold M., Thoenen H. Experimental hypertension of the rat: reciprocal changes of norepinephrine turnover in heart and brain-stem. Naunyn Schmiedebergs Arch Pharmakol. 1971;268(2):125–139. doi: 10.1007/BF01020067. [DOI] [PubMed] [Google Scholar]
  28. Palkovits M., Záborszky L. Neuroanatomy of central cardiovascular control. Nucleus tractus solitarii: afferent and efferent neuronal connections in relation to the baroreceptor reflex arc. Prog Brain Res. 1977;47:9–34. doi: 10.1016/S0079-6123(08)62709-0. [DOI] [PubMed] [Google Scholar]
  29. Reed D. J., Withrow C. D., Woodbury D. M. Electrolyte and acid-base parameters of rat cerebrospinal fluid. Exp Brain Res. 1967;3(3):212–219. doi: 10.1007/BF00235585. [DOI] [PubMed] [Google Scholar]
  30. Ricksten S. E., Thorén P. Reflex control of sympathetic nerve activity and heart rate from arterial baroreceptors in conscious spontaneously hypertensive rats. Clin Sci (Lond) 1981 Dec;61 (Suppl 7):169s–172s. doi: 10.1042/cs061169s. [DOI] [PubMed] [Google Scholar]
  31. Sasaki S., Buñag R. D. Hypothalamic lesions abolish cardiovascular responses to chronic saline ingestion. Am J Physiol. 1983 Jun;244(6):R751–R757. doi: 10.1152/ajpregu.1983.244.6.R751. [DOI] [PubMed] [Google Scholar]
  32. Sleight P., West M. J., Korner P. I., Oliver J. R., Chalmers J. P., Robinson J. L. The action of clonidine on the baroreflex control of heart rate in conscious animals and man, and on single aortic baroreceptor discharge in the rabbit. Arch Int Pharmacodyn Ther. 1975 Mar;214(1):4–11. [PubMed] [Google Scholar]
  33. Spyer K. M. Baroreceptor sensitive neurones in the anterior hypothalamus of the cat. J Physiol. 1972 Jul;224(1):245–257. doi: 10.1113/jphysiol.1972.sp009892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Summy-Long J. Y., Rosella L. M., Keil L. C. Effects of centrally administered endogenous opioid peptides on drinking behavior, increased plasma vasopressin concentration and pressor response to hypertonic sodium chloride. Brain Res. 1981 Sep 28;221(2):343–357. doi: 10.1016/0006-8993(81)90783-6. [DOI] [PubMed] [Google Scholar]
  35. Takeda K., Buñag R. D. Sympathetic hyperactivity during hypothalamic stimulation in spontaneously hypertensive rats. J Clin Invest. 1978 Sep;62(3):642–648. doi: 10.1172/JCI109171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Takeshita A., Tanaka S., Kuroiwa A., Nakamura M. Reduced baroreceptor sensitivity in borderline hypertension. Circulation. 1975 Apr;51(4):738–742. doi: 10.1161/01.cir.51.4.738. [DOI] [PubMed] [Google Scholar]
  37. Thrasher T. N., Brown C. J., Keil L. C., Ramsay D. J. Thirst and vasopressin release in the dog: an osmoreceptor or sodium receptor mechanism? Am J Physiol. 1980 May;238(5):R333–R339. doi: 10.1152/ajpregu.1980.238.5.R333. [DOI] [PubMed] [Google Scholar]
  38. Toal C. B., Sunahara F. A. Effects of central stimulation on reflex bradycardia in the spontaneously hypertensive rat. Clin Exp Hypertens A. 1982;4(3):393–410. doi: 10.3109/10641968209060751. [DOI] [PubMed] [Google Scholar]
  39. van Ameringen M. R., de Champlain J., Imbeault S. Participation of central noradrenergic neurons in experimental hypertension. Can J Physiol Pharmacol. 1977 Dec;55(6):1246–1251. doi: 10.1139/y77-170. [DOI] [PubMed] [Google Scholar]

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