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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1996 Nov 1;98(9):2060–2065. doi: 10.1172/JCI119011

Atrial natriuretic peptide regulation of noradrenaline release in the anterior hypothalamic area of spontaneously hypertensive rats.

N Peng 1, S Oparil 1, Q C Meng 1, J M Wyss 1
PMCID: PMC507650  PMID: 8903325

Abstract

In spontaneously hypertensive rats (SHR), high NaCl diets increase arterial pressure and sympathetic nervous system activity by decreasing noradrenaline release in the anterior hypothalamic area (AHA), thereby reducing the activation of sympathoinhibitory neurons in AHA. Atrial natriuretic peptide (ANP) can inhibit the release of noradrenaline, and ANP concentration is elevated in the AHA of SHR. The present study tests the hypothesis that in SHR, local ANP inhibits noradrenaline release from nerve terminals in AHA. Male SHR fed a basal or high NaCl diet for 2 wk and normotensive Wistar Kyoto rats (WKY) fed a basal NaCl diet were studied. In SHR on the basal diet, microperfusion of exogenous ANP into the AHA elicited a dose-related decrease in the concentration of the major noradrenaline metabolite 3-methoxy-4-hydroxy-phenylglycol (MOPEG) in the AHA; this effect was attenuated in the other two groups. In a subsequent study, the ANP-C (clearance) receptor agonist c-ANP was microperfused into the AHA to increase extracellular concentration of endogenous ANP in AHA. c-ANP reduced AHA MOPEG concentration in SHR on the basal NaCl diet but not in the other two groups. These data support the hypothesis that local ANP inhibits noradrenaline release in the AHA and thereby contributes to NaCl-sensitive hypertension in SHR.

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Selected References

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  1. Brenner B. M., Ballermann B. J., Gunning M. E., Zeidel M. L. Diverse biological actions of atrial natriuretic peptide. Physiol Rev. 1990 Jul;70(3):665–699. doi: 10.1152/physrev.1990.70.3.665. [DOI] [PubMed] [Google Scholar]
  2. Casto R., Hilbig J., Schroeder G., Stock G. Atrial natriuretic factor inhibits central angiotensin II pressor responses. Hypertension. 1987 May;9(5):473–477. doi: 10.1161/01.hyp.9.5.473. [DOI] [PubMed] [Google Scholar]
  3. Chen C. W., Chen Y. F., Meng Q. C., Wyss J. M., Oparil S. Decreased norepinephrine release in anterior hypothalamus of NaCl-sensitive spontaneously hypertensive rats during high NaCl intake. Brain Res. 1991 Nov 22;565(1):135–141. doi: 10.1016/0006-8993(91)91744-l. [DOI] [PubMed] [Google Scholar]
  4. Cuadra G., Summers K., Giacobini E. Cholinesterase inhibitor effects on neurotransmitters in rat cortex in vivo. J Pharmacol Exp Ther. 1994 Jul;270(1):277–284. [PubMed] [Google Scholar]
  5. Drewett J. G., Trachte G. J., Marchand G. R. Atrial natriuretic factor inhibits adrenergic and purinergic neurotransmission in the rabbit isolated vas deferens. J Pharmacol Exp Ther. 1989 Jan;248(1):135–142. [PubMed] [Google Scholar]
  6. Ermirio R., Ruggeri P., Cogo C. E., Molinari C., Bergaglio M., Calaresu F. R. The role of ANF in functional properties of the central pathways of cardiovascular reflexes. J Auton Nerv Syst. 1990 Jul;30 (Suppl):S51–S53. doi: 10.1016/0165-1838(90)90101-n. [DOI] [PubMed] [Google Scholar]
  7. FOLKOW B., JOHANSSON B., OBERG B. A hypothalamic structure with a marked inhibitory effect on tonic sympathetic activity. Acta Physiol Scand. 1959 Nov 15;47:262–270. doi: 10.1111/j.1748-1716.1960.tb00077.x. [DOI] [PubMed] [Google Scholar]
  8. Fernandez B. E., Vatta M. S., Bianciotti L. G. Comparative effects of bradykinin and atrial natriuretic factor on neuronal and non-neuronal noradrenaline uptake in the central nervous system of the rat. Arch Int Physiol Biochim Biophys. 1993 Nov-Dec;101(6):337–340. doi: 10.3109/13813459309046989. [DOI] [PubMed] [Google Scholar]
  9. Floras J. S. Inhibitory effect of atrial natriuretic factor on sympathetic ganglionic neurotransmission in humans. Am J Physiol. 1995 Aug;269(2 Pt 2):R406–R412. doi: 10.1152/ajpregu.1995.269.2.R406. [DOI] [PubMed] [Google Scholar]
  10. Holtz J., Münzel T., Sommer O., Bassenge E. Sympathoadrenal inhibition by atrial natriuretic peptide is not attenuated during development of congestive heart failure in dogs. Circulation. 1989 Dec;80(6):1862–1869. doi: 10.1161/01.cir.80.6.1862. [DOI] [PubMed] [Google Scholar]
  11. Howe P. R. Blood pressure control by neurotransmitters in the medulla oblongata and spinal cord. J Auton Nerv Syst. 1985 Feb-Mar;12(2-3):95–115. doi: 10.1016/0165-1838(85)90054-2. [DOI] [PubMed] [Google Scholar]
  12. Jin H. K., Chen Y. F., Yang R. H., Meng Q. C., Oparil S. Impaired release of atrial natriuretic factor in NaCl-loaded spontaneously hypertensive rats. Hypertension. 1988 Jun;11(6 Pt 2):739–744. doi: 10.1161/01.hyp.11.6.739. [DOI] [PubMed] [Google Scholar]
  13. Jin H. K., Yang R. H., Chen Y. F., Wyss J. M., Oparil S. Altered stores of atrial natriuretic peptide in specific brain nuclei of NaCl-sensitive spontaneously hypertensive rats. Am J Hypertens. 1991 May;4(5 Pt 1):449–455. doi: 10.1093/ajh/4.5.449. [DOI] [PubMed] [Google Scholar]
  14. Jin H. K., Yang R. H., Chen Y. F., Wyss J. M., Oparil S. Altered stores of atrial natriuretic peptide in specific brain nuclei of NaCl-sensitive spontaneously hypertensive rats. Am J Hypertens. 1991 May;4(5 Pt 1):449–455. doi: 10.1093/ajh/4.5.449. [DOI] [PubMed] [Google Scholar]
  15. Jin H., Yang R. H., Calhoun D. A., Wyss J. M., Oparil S. Atrial natriuretic peptide modulates baroreceptor reflex in spontaneously hypertensive rat. Hypertension. 1992 Sep;20(3):374–379. doi: 10.1161/01.hyp.20.3.374. [DOI] [PubMed] [Google Scholar]
  16. John A. E., Morich F. J. ANP concentrations of atria, plasma and brain in Dahl S (DS) and Dahl R (DR) rats. Clin Exp Hypertens A. 1990;12(2):191–204. doi: 10.3109/10641969009074728. [DOI] [PubMed] [Google Scholar]
  17. Lang C. C., Choy A. M., Balfour D. J., Struthers A. D. Prazosin attenuates the natriuretic response to atrial natriuretic factor in man. Kidney Int. 1992 Aug;42(2):433–441. doi: 10.1038/ki.1992.306. [DOI] [PubMed] [Google Scholar]
  18. Marrocco R. T., Lane R. F., McClurkin J. W., Blaha C. D., Alkire M. F. Release of cortical catecholamines by visual stimulation requires activity in thalamocortical afferents of monkey and cat. J Neurosci. 1987 Sep;7(9):2756–2767. doi: 10.1523/JNEUROSCI.07-09-02756.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nakamaru M., Inagami T. Atrial natriuretic factor inhibits norepinephrine release evoked by sympathetic nerve stimulation in isolated perfused rat mesenteric arteries. Eur J Pharmacol. 1986 Apr 29;123(3):459–461. doi: 10.1016/0014-2999(86)90724-7. [DOI] [PubMed] [Google Scholar]
  20. Nakamura K., Nakamura S., Hojyo A., Nakanishi K. Effect of saline loading on ANP in the cerebrospinal fluid of rats. Nihon Jinzo Gakkai Shi. 1992 Jan;34(1):27–31. [PubMed] [Google Scholar]
  21. Peng N., Meng Q. C., King K., Oparil S., Wyss J. M. Acute hypertension increases norepinephrine release in the anterior hypothalamic area. Hypertension. 1995 Apr;25(4 Pt 2):828–833. doi: 10.1161/01.hyp.25.4.828. [DOI] [PubMed] [Google Scholar]
  22. Peng N., Meng Q. C., Oparil S., Wyss J. M. Acute saline infusion decreases norepinephrine release in the anterior hypothalamic area. Hypertension. 1996 Mar;27(3 Pt 2):578–583. doi: 10.1161/01.hyp.27.3.578. [DOI] [PubMed] [Google Scholar]
  23. Phillips M. I., Kimura B., Wang H., Hoffman W. E. Effect of vagotomy on brain and plasma atrial natriuretic peptide during hemorrhage. Am J Physiol. 1989 Dec;257(6 Pt 2):R1393–R1399. doi: 10.1152/ajpregu.1989.257.6.R1393. [DOI] [PubMed] [Google Scholar]
  24. Shibata K., Sakimura M., Furukawa T. Antagonism of central pressor response to angiotensin II by alpha-human atrial natriuretic polypeptide at the preoptic area and posterior hypothalamus in rats. Neuropharmacology. 1993 Feb;32(2):175–184. doi: 10.1016/0028-3908(93)90098-n. [DOI] [PubMed] [Google Scholar]
  25. Simon O. R., Basuray B. N., West W. L., Copeland R. Interaction between the baroreflex and anterior hypothalamic stimulation. Demonstration of a noradrenergic involvement. Neuropharmacology. 1985 Jul;24(7):665–675. doi: 10.1016/0028-3908(85)90110-8. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Stepniakowski K., Budzikowski A., Loń S., Szczepańska-Sadowska E. Central cardiovascular effects of AVP and ANP in normotensive and spontaneously hypertensive rats. J Auton Nerv Syst. 1994 Apr;47(1-2):33–43. doi: 10.1016/0165-1838(94)90063-9. [DOI] [PubMed] [Google Scholar]
  28. Takayanagi R., Grammer R. T., Inagami T. Regional increase of cyclic GMP by atrial natriuretic factor in rat brain: markedly elevated response in spontaneously hypertensive rats. Life Sci. 1986 Aug 11;39(6):573–580. doi: 10.1016/0024-3205(86)90515-1. [DOI] [PubMed] [Google Scholar]
  29. Thornton R. M., Wyss J. M., Oparil S. Impaired reflex response to volume expansion in NaCl-sensitive spontaneously hypertensive rats. Hypertension. 1989 Nov;14(5):518–523. doi: 10.1161/01.hyp.14.5.518. [DOI] [PubMed] [Google Scholar]
  30. Tremblay J., Huot C., Willenbrock R. C., Bayard F., Gossard F., Fujio N., Koch C., Kuchel O., Debinski W., Hamet P. Increased cyclic guanosine monophosphate production and overexpression of atrial natriuretic peptide A-receptor mRNA in spontaneously hypertensive rats. J Clin Invest. 1993 Nov;92(5):2499–2508. doi: 10.1172/JCI116858. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Vatta M., Travaglianti M., Bianciotti L., Coll C., Perazzo J., Fernández B. Atrial natriuretic factor effects on norepinephrine uptake in discrete telencephalic and diencephalic nuclei of the rat. Brain Res. 1994 May 23;646(2):324–326. doi: 10.1016/0006-8993(94)90099-x. [DOI] [PubMed] [Google Scholar]
  32. Wyss J. M., Yang R. H., Jin H. K., Oparil S. Hypothalamic microinjection of alpha 2-adrenoceptor agonists causes greater sympathoinhibition in spontaneously hypertensive rats on high NaCl diets. J Hypertens. 1988 Oct;6(10):805–813. [PubMed] [Google Scholar]
  33. Yang R. H., Jin H. K., Chen Y. F., Wyss J. M., Oparil S. Blockade of endogenous anterior hypothalamic atrial natriuretic peptide with monoclonal antibody lowers blood pressure in spontaneously hypertensive rats. J Clin Invest. 1990 Dec;86(6):1985–1990. doi: 10.1172/JCI114933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Yang R. H., Jin H. K., Wyss J. M., Chen Y. F., Oparil S. Pressor effect of blocking atrial natriuretic peptide in nucleus tractus solitarii. Hypertension. 1992 Feb;19(2):198–205. doi: 10.1161/01.hyp.19.2.198. [DOI] [PubMed] [Google Scholar]
  35. Zsilla G., Zelles T., Mike A., Kékes-Szabó A., Milusheva E., Vizi E. S. Differential changes in presynaptic modulation of transmitter release during aging. Int J Dev Neurosci. 1994 Apr;12(2):107–115. doi: 10.1016/0736-5748(94)90003-5. [DOI] [PubMed] [Google Scholar]

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