Skip to main content
SpringerLink
Log in

Contribution of Baroreflex Afferent Pathway to NPY-Mediated Regulation of Blood Pressure in Rats

  • Original Article
  • Published:
Neuroscience Bulletin Aims and scope Submit manuscript

Abstract

Neuropeptide Y (NPY), a metabolism-related cardiovascular factor, plays a crucial role in blood pressure (BP) regulation via peripheral and central pathways. The expression of NPY receptors (Y1R/Y2R) specific to baroreflex afferents impacts on the sexually dimorphic neural control of circulation. This study was designed to investigate the expression profiles of NPY receptors in the nodose ganglion (NG) and nucleus tractus solitary (NTS) under hypertensive conditions. To this end, rats with hypertension induced by NG-nitro-L-arginine methylester (L-NAME) or high fructose drinking (HFD), and spontaneously hypertensive rats (SHRs) were used to explore the effects/mechanisms of NPY on BP using functional, molecular, and electrophysiological approaches. The data showed that BP was elevated along with baroreceptor sensitivity dysfunction in model rats; Y1R was up- or down-regulated in the NG or NTS of male and female HFD/L-NAME groups, while Y2R was only down-regulated in the HFD groups as well as in the NG of the male L-NAME group. In SHRs, Y1R and Y2R were both down-regulated in the NTS, and not in the NG. In addition to NPY-mediated energy homeostasis, leptin-melanocortin activation may be essential for metabolic disturbance-related hypertension. We found that leptin and α-melanocyte stimulating hormone (α-MSH) receptors were aberrantly down-regulated in HFD rats. In addition, α-MSH concentrations were reduced and NPY concentrations were elevated in the serum and NTS at 60 and 90 min after acute leptin infusion. Electrophysiological recordings showed that the decay time-constant and area under the curve of excitatory post-synaptic currents were decreased by Y1R activation in A-types, whereas, both were increased by Y2R activation in Ah- or C-types. These results demonstrate that sex- and afferent-specific NPY receptor expression in the baroreflex afferent pathway is likely to be a novel target for the clinical management of metabolism-related and essential hypertension.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Tatemoto K, Carlquist M, Mutt V. Neuropeptide Y–a novel brain peptide with structural similarities to peptide YY and pancreatic polypeptide. Nature 1982, 296: 659–660.

    CAS  PubMed  Google Scholar 

  2. Lang UE, Beglinger C, Schweinfurth N, Walter M, Borgwardt S. Nutritional aspects of depression. Cell Physiol Biochem 2015, 37: 1029–1043.

    CAS  PubMed  Google Scholar 

  3. Bouret SG. Development of Hypothalamic Circuits That Control Food Intake and Energy Balance. In: Harris RBS (Ed.). Appetite and Food Intake: Central Control. Boca Raton (FL): CRC Press/Taylor & Francis, 2017: 135–154.

    Google Scholar 

  4. Loh K, Herzog H, Shi YC. Regulation of energy homeostasis by the NPY system. Trends Endocrinol Metab 2015, 26: 125–135.

    CAS  PubMed  Google Scholar 

  5. Jacques D, Abdel-Samad D. Neuropeptide Y (NPY) and NPY receptors in the cardiovascular system: implication in the regulation of intracellular calcium. Can J Physiol Pharmacol 2007, 85: 43–53.

    CAS  PubMed  Google Scholar 

  6. Kennedy B, Shen GH, Ziegler MG. Neuropeptide Y-mediated pressor responses following high-frequency stimulation of the rat sympathetic nervous system. J Pharmacol Exp Ther 1997, 281: 291–296.

    CAS  PubMed  Google Scholar 

  7. Cheng PW, Wu AT, Lu PJ, Yang YC, Ho WY, Lin HC, et al. Central hypotensive effects of neuropeptide Y are modulated by endothelial nitric oxide synthase after activation by ribosomal protein S6 kinase. Br J Pharmacol 2012, 167: 1148–1160.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Wahlestedt C, Yanaihara N, Hakanson R. Evidence for different pre-and post-junctional receptors for neuropeptide Y and related peptides. Regul Pept 1986, 13: 307–318.

    CAS  PubMed  Google Scholar 

  9. Liu Y, Wu D, Qu MY, He JL, Yuan M, Zhao M, et al. Neuropeptide Y-mediated sex- and afferent-specific neurotransmissions contribute to sexual dimorphism of baroreflex afferent function. Oncotarget 2016, 7: 66135–66148.

    PubMed  PubMed Central  Google Scholar 

  10. Barraco RA, Ergene E, Dunbar JC, Ganduri YL, Anderson GF. Y2 receptors for neuropeptide Y in the nucleus of the solitary tract mediate depressor responses. Peptides 1991, 12: 691–698.

    CAS  PubMed  Google Scholar 

  11. Mankin LA. Update in hypertension therapy. Med Clin North Am 2016, 100: 665–693.

    PubMed  Google Scholar 

  12. Tu H, Zhang D, Li YL. Cellular and molecular mechanisms underlying arterial baroreceptor remodeling in cardiovascular diseases and diabetes. Neurosci Bull 2019, 35: 98–112.

    CAS  PubMed  Google Scholar 

  13. Potje SR, Munhoz FC, Perassa LA, Graton ME, Pereira AA, Nakamune AC, et al. Mechanisms underlying the hypotensive and vasodilator effects of Ru(terpy)(bdq)NO](3 +), a nitric oxide donor, differ between normotensive and spontaneously hypertensive rats. Eur J Pharmacol 2014, 741: 222–229.

    CAS  PubMed  Google Scholar 

  14. Yi M, Li H, Wu Z, Yan J, Liu Q, Ou C, et al. A promising therapeutic target for metabolic diseases: neuropeptide Y receptors in humans. Cell Physiol Biochem 2018, 45: 88–107.

    CAS  PubMed  Google Scholar 

  15. Zemancikova A, Torok J. Cardiovascular effects of high-fructose intake in rats with nitric oxide deficiency. Interdiscip Toxicol 2014, 7: 159–164.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Cyr NE, Toorie AM, Steger JS, Sochat MM, Hyner S, Perello M, et al. Mechanisms by which the orexigen NPY regulates anorexigenic alpha-MSH and TRH. Am J Physiol Endocrinol Metab 2013, 304: E640–650.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. do Carmo JM, da Silva AA, Freeman JN, Wang Z, Moak SP, Hankins MW, et al. Neuronal suppressor of cytokine signaling 3: Role in modulating chronic metabolic and cardiovascular effects of leptin. Hypertension 2018, 71: 1248–1257.

    PubMed  PubMed Central  Google Scholar 

  18. Andresen MC, Kunze DL. Nucleus tractus solitarius–gateway to neural circulatory control. Annu Rev Physiol 1994, 56: 93–116.

    CAS  PubMed  Google Scholar 

  19. Browning KN. Excitability of nodose ganglion cells and their role in vago-vagal reflex control of gastrointestinal function. Curr Opin Pharmacol 2003, 3: 613–617.

    CAS  PubMed  Google Scholar 

  20. Kawai Y, Senba E. Organization of excitatory and inhibitory local networks in the caudal nucleus of tractus solitarius of rats revealed in in vitro slice preparation. J Comp Neurol 1996, 373: 309–321.

    CAS  PubMed  Google Scholar 

  21. Lachamp P, Balland B, Tell F, Crest M, Kessler JP. Synaptic localization of the glutamate receptor subunit GluR2 in the rat nucleus tractus solitarii. Eur J Neurosci 2003, 17: 892–896.

    PubMed  Google Scholar 

  22. Travagli RA, Hermann GE, Browning KN, Rogers RC. Brainstem circuits regulating gastric function. Annu Rev Physiol 2006, 68: 279–305.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Jin YH, Bailey TW, Li BY, Schild JH, Andresen MC. Purinergic and vanilloid receptor activation releases glutamate from separate cranial afferent terminals in nucleus tractus solitarius. J Neurosci 2004, 24: 4709–4717.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Baltazi M, Katsiki N, Savopoulos C, Iliadis F, Koliakos G, Hatzitolios AI. Plasma neuropeptide Y (NPY) and alpha-melanocyte stimulating hormone (a-MSH) levels in patients with or without hypertension and/or obesity: a pilot study. Am J Cardiovasc Dis 2011, 1: 48–59.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Mountjoy KG, Mortrud MT, Low MJ, Simerly RB, Cone RD. Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain. Mol Endocrinol 1994, 8: 1298–1308.

    CAS  PubMed  Google Scholar 

  26. Matsumura K, Tsuchihashi T, Fujii K, Iida M. Neural regulation of blood pressure by leptin and the related peptides. Regul Pept 2003, 114: 79–86.

    CAS  PubMed  Google Scholar 

  27. Puzserova A, Bernatova I. Blood pressure regulation in stress: focus on nitric oxide-dependent mechanisms. Physiol Res 2016, 65: S309–S342.

    CAS  PubMed  Google Scholar 

  28. Lim K, Barzel B, Burke SL, Armitage JA, Head GA. Origin of aberrant blood pressure and sympathetic regulation in diet-induced obesity. Hypertension 2016, 68: 491–500.

    CAS  PubMed  Google Scholar 

  29. Barzel B, Lim K, Davern PJ, Burke SL, Armitage JA, Head GA. Central proopiomelanocortin but not neuropeptide Y mediates sympathoexcitation and hypertension in fat fed conscious rabbits. J Hypertens 2016, 34: 464–473; discussion 473.

    CAS  PubMed  Google Scholar 

  30. Krukoff TL, MacTavish D, Jhamandas JH. Effects of restraint stress and spontaneous hypertension on neuropeptide Y neurones in the brainstem and arcuate nucleus. J Neuroendocrinol 1999, 11: 715–723.

    CAS  PubMed  Google Scholar 

  31. Guo XW, Wang XL, Gao ZL. Effect of neuropeptide Y and neurotensin on diurnal rhythm of blood pressure and target organ damage for essential hypertension. Zhonghua Xin Xue Guan Bing Za Zhi 2005, 33: 1006–1009.

    CAS  PubMed  Google Scholar 

  32. He JL, Zhao M, Xia JJ, Guan J, Liu Y, Wang LQ, et al. FGF21 ameliorates the neurocontrol of blood pressure in the high fructose-drinking rats. Sci Rep 2016, 6: 29582.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Li BY, Glazebrook P, Kunze DL, Schild JH. KCa1.1 channel contributes to cell excitability in unmyelinated but not myelinated rat vagal afferents. Am J Physiol Cell Physiol 2011, 300: C1393–1403.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Geiger JR, Jonas P. Dynamic control of presynaptic Ca(2 +) inflow by fast-inactivating K(+) channels in hippocampal mossy fiber boutons. Neuron 2000, 28: 927–939.

    CAS  PubMed  Google Scholar 

  35. Sabatini BL, Regehr WG. Control of neurotransmitter release by presynaptic waveform at the granule cell to Purkinje cell synapse. J Neurosci 1997, 17: 3425–3435.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Mendelowitz D, Kunze DL. Characterization of calcium currents in aortic baroreceptor neurons. J Neurophysiol 1992, 68: 509–517.

    CAS  PubMed  Google Scholar 

  37. Mendelowitz D, Reynolds PJ, Andresen MC. Heterogeneous functional expression of calcium channels at sensory and synaptic regions in nodose neurons. J Neurophysiol 1995, 73: 872–875.

    CAS  PubMed  Google Scholar 

  38. Blakemore LJ, Levenson CW, Trombley PQ. Neuropeptide Y modulates excitatory synaptic transmission in the olfactory bulb. Neuroscience 2006, 138: 663–674.

    CAS  PubMed  Google Scholar 

  39. Harper AA. Similarities between some properties of the soma and sensory receptors of primary afferent neurones. Exp Physiol 1991, 76: 369–377.

    CAS  PubMed  Google Scholar 

  40. Shih CD, Chan JY, Chan SH. Tonic suppression of baroreceptor reflex response by endogenous neuropeptide Y at the nucleus tractus solitarius of the rat. Neurosci Lett 1992, 148: 169–172.

    CAS  PubMed  Google Scholar 

  41. Matsumura K, Tsuchihashi T, Abe I, Iida M. Central alpha-melanocyte-stimulating hormone acts at melanocortin-4 receptor to activate sympathetic nervous system in conscious rabbits. Brain Res 2002, 948: 145–148.

    CAS  PubMed  Google Scholar 

  42. Rahmouni K, Correia ML, Haynes WG, Mark AL. Obesity-associated hypertension: new insights into mechanisms. Hypertension 2005, 45: 9–14.

    CAS  PubMed  Google Scholar 

  43. Lembo G, Vecchione C, Fratta L, Marino G, Trimarco V, d’Amati G, et al. Leptin induces direct vasodilation through distinct endothelial mechanisms. Diabetes 2000, 49: 293–297.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (31171122, 81573431, 81773731, 81971326, and 8190130222).

Author information

Author notes

  1. Yang Liu and Shu-Yang Zhao have contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacology, State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin, 150081, China

    Yang Liu, Shu-Yang Zhao, Yan Feng, Jie Sun, Qiu-Xin Yan, Ying Li, Zhuo Liu, Lu-Qi Wang, Xun Sun, Guo-Fen Qiao & Bai-Yan Li

  2. Department of Clinical Laboratory, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China

    Yang Liu & Shijun Li

  3. Department of Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, 116044, China

    Xiao-Long Lu

  4. Riley Heart Center, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Zhuo Liu

Authors
  1. Yang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shu-Yang Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yan Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jie Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiao-Long Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qiu-Xin Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ying Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zhuo Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lu-Qi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Xun Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Shijun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Guo-Fen Qiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Bai-Yan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Guo-Fen Qiao or Bai-Yan Li.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 742 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, Y., Zhao, SY., Feng, Y. et al. Contribution of Baroreflex Afferent Pathway to NPY-Mediated Regulation of Blood Pressure in Rats. Neurosci. Bull. 36, 396–406 (2020). https://doi.org/10.1007/s12264-019-00438-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12264-019-00438-w

Keywords

Search

Navigation