Display options
Cite
Domingos-Souza G, Santos-Almeida FM, Meschiari CA, et al. The ability of baroreflex activation to improve blood pressure and resistance vessel function in spontaneously hypertensive rats is dependent on stimulation parameters. Hypertens Res. 2021;44(8):932-940doi: 10.1038/s41440-021-00639-9.
Domingos-Souza, G., Santos-Almeida, F. M., Meschiari, C. A., Ferreira, N. S., Pereira, C. A., Pestana-Oliveira, N., Prates-Costa, T. C., Tostes, R. C., White, C., & Fazan, R. (2021). The ability of baroreflex activation to improve blood pressure and resistance vessel function in spontaneously hypertensive rats is dependent on stimulation parameters. Hypertension research : official journal of the Japanese Society of Hypertension, 44(8), 932-940. https://doi.org/10.1038/s41440-021-00639-9
Domingos-Souza, Gean, et al. "The ability of baroreflex activation to improve blood pressure and resistance vessel function in spontaneously hypertensive rats is dependent on stimulation parameters." Hypertension research : official journal of the Japanese Society of Hypertension vol. 44,8 (2021): 932-940. doi: https://doi.org/10.1038/s41440-021-00639-9
Domingos-Souza G, Santos-Almeida FM, Meschiari CA, Ferreira NS, Pereira CA, Pestana-Oliveira N, Prates-Costa TC, Tostes RC, White C, Fazan R. The ability of baroreflex activation to improve blood pressure and resistance vessel function in spontaneously hypertensive rats is dependent on stimulation parameters. Hypertens Res. 2021 Aug;44(8):932-940. doi: 10.1038/s41440-021-00639-9. Epub 2021 Mar 12. PMID: 33707760.
Copy Download .nbib Format: NLM
Share it on

Hypertens Res. 2021 Aug;44(8):932-940. doi: 10.1038/s41440-021-00639-9. Epub 2021 Mar 12.

The ability of baroreflex activation to improve blood pressure and resistance vessel function in spontaneously hypertensive rats is dependent on stimulation parameters.

Hypertension research : official journal of the Japanese Society of Hypertension

Gean Domingos-Souza, Fernanda Machado Santos-Almeida, Cesar Arruda Meschiari, Nathanne S Ferreira, Camila A Pereira, Nayara Pestana-Oliveira, Thaís Caroline Prates-Costa, Rita C Tostes, Carl White, Rubens Fazan

Affiliations

  1. Physiology and Biophysics, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA. [email protected].
  2. Department of Physiology, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. [email protected].
  3. Department of Physiology, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
  4. Health and Sports Science Center, Federal University of Acre, Rio Branco, AC, Brazil.
  5. Department of Pharmacology, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
  6. Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN, USA.
  7. Physiology and Biophysics, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.

PMID: 33707760 DOI: 10.1038/s41440-021-00639-9

Abstract

Baroreflex activation by electric stimulation of the carotid sinus (CS) effectively lowers blood pressure. However, the degree to which differences between stimulation protocols impinge on cardiovascular outcomes has not been defined. To address this, we examined the effects of short- and long-duration (SD and LD) CS stimulation on hemodynamic and vascular function in spontaneously hypertensive rats (SHRs). We fit animals with miniature electrical stimulators coupled to electrodes positioned around the left CS nerve that delivered intermittent 5/25 s ON/OFF (SD) or 20/20 s ON/OFF (LD) square pulses (1 ms, 3 V, 30 Hz) continuously applied for 48 h in conscious animals. A sham-operated control group was also studied. We measured mean arterial pressure (MAP), systolic blood pressure variability (SBPV), heart rate (HR), and heart rate variability (HRV) for 60 min before stimulation, 24 h into the protocol, and 60 min after stimulation had stopped. SD stimulation reversibly lowered MAP and HR during stimulation. LD stimulation evoked a decrease in MAP that was sustained even after stimulation was stopped. Neither SD nor LD had any effect on SBPV or HRV when recorded after stimulation, indicating no adaptation in autonomic activity. Both the contractile response to phenylephrine and the relaxation response to acetylcholine were increased in mesenteric resistance vessels isolated from LD-stimulated rats only. In conclusion, the ability of baroreflex activation to modulate hemodynamics and induce lasting vascular adaptation is critically dependent on the electrical parameters and duration of CS stimulation.

© 2021. The Author(s), under exclusive licence to The Japanese Society of Hypertension.

Keywords: Baroreceptors; Carotid sinus; Hypertension; Mesenteric resistance arterioles.; Sympathetic activity

References

  1. Seravalle G, Dell’Oro R, Grassi G. Baroreflex activation therapy systems: current status and future prospects. Expert Rev Med Devices. 2019;16:1025–33. - PubMed
  2. Bisognano JD, Bakris G, Nadim MK, Sanchez L, Kroon AA, Schafer J, et al. Baroreflex activation therapy lowers blood pressure in patients with resistant hypertension: results from the double-blind, randomized, placebo-controlled rheos pivotal trial. J Am Coll Cardiol. 2011;58:765–73. - PubMed
  3. Illig KA, Levy M, Sanchez L, Trachiotis GD, Shanley C, Irwin E, et al. An implantable carotid sinus stimulator for drug-resistant hypertension: surgical technique and short-term outcome from the multicenter phase II Rheos feasibility trial. J Vasc Surg. 2006;44:1213–8. - PubMed
  4. de Leeuw PW, Alnima T, Lovett E, Sica D, Bisognano J, Haller H, et al. Bilateral or unilateral stimulation for baroreflex activation therapy. Hypertension. 2015;65:187–92. - PubMed
  5. Tordoir JHM, Scheffers I, Schmidli J, Savolainen H, Liebeskind U, Hansky B, et al. An implantable carotid sinus baroreflex activating system: surgical technique and short-term outcome from a multi-center feasibility trial for the treatment of resistant hypertension. Eur J Vasc Endovasc Surg. 2007;33:414–21. - PubMed
  6. Wustmann K, Kucera JP, Scheffers I, Mohaupt M, Kroon AA, de Leeuw PW, et al. Effects of chronic baroreceptor stimulation on the autonomic cardiovascular regulation in patients with drug-resistant arterial hypertension. Hypertension. 2009;54:530–6. - PubMed
  7. Abraham WT, Zile MR, Weaver FA, Butter C, Ducharme A, Halbach M, et al. Baroreflex activation therapy for the treatment of heart failure with a reduced ejection fraction. JACC Heart Fail. 2015;3:487–96. - PubMed
  8. Gronda E, Seravalle G, Brambilla G, Costantino G, Casini A, Alsheraei A, et al. Chronic baroreflex activation effects on sympathetic nerve traffic, baroreflex function, and cardiac haemodynamics in heart failure: a proof-of-concept study. Eur J Heart Fail. 2014;16:977–83. - PubMed
  9. Alnima T, Scheffers I, De Leeuw PW, Winkens B, Jongen-Vancraybex H, Tordoir JH, et al. Sustained acute voltage-dependent blood pressure decrease with prolonged carotid baroreflex activation in therapy-resistant hypertension. J Hypertens. 2012;30:1665–70. - PubMed
  10. Heusser K, Tank J, Engeli S, Diedrich A, Menne J, Eckert S, et al. Carotid baroreceptor stimulation, sympathetic activity, baroreflex function, and blood pressure in hypertensive patients. Hypertension. 2010;55:619–26. - PubMed
  11. Mancia G, Grassi G. The autonomic nervous system and hypertension. Circ Res. 2014;114:1804–14. - PubMed
  12. Yoruk A, Bisognano JD, Gassler JP. Baroreceptor stimulation for resistant hypertension. Am J Hypertens. 2016;29:1319–24. - PubMed
  13. Lohmeier TE, Irwin ED, Rossing MA, Serdar DJ, Kieval RS. Prolonged activation of the baroreflex produces sustained hypotension. Hypertension. 2004;43:306–11. - PubMed
  14. Lohmeier TE, Dwyer TM, Hildebrandt DA, Irwin ED, Rossing MA, Serdar DJ, et al. Influence of prolonged baroreflex activation on arterial pressure in angiotensin hypertension. Hypertension. 2005;46:1194–1200. - PubMed
  15. Lohmeier TE, Hildebrandt DA, Dwyer TM, Iliescu R, Irwin ED, Cates AW, et al. Prolonged activation of the baroreflex decreases arterial pressure even during chronic adrenergic blockade. Hypertension. 2009;53:833–8. - PubMed
  16. Lohmeier TE, Hildebrandt DA, Dwyer TM, Barrett AM, Irwin ED, Rossing MA, et al. Renal denervation does not abolish sustained baroreflex-mediated reductions in arterial pressure. Hypertension. 2007;49:373–9. - PubMed
  17. Lohmeier TE, Iliescu R. Chronic lowering of blood pressure by carotid baroreflex activation: mechanisms and potential for hypertension therapy. Hypertension. 2011;57:880–6. - PubMed
  18. Judy WV, Watanabe AM, Murphy WR, Aprison BS, Yu PL. Sympathetic nerve activity and blood pressure in normotensive backcross rats genetically related to the spontaneously hypertensive rat. Hypertension. 1979;1:598–604. - PubMed
  19. Yamori Y, Okamoto K. Hypothalamic tonic regulation of blood pressure in spontaneously hypertensive rats. Jpn Circ J. 1969;33:509–19. - PubMed
  20. Courand P-Y, Feugier P, Workineh S, Harbaoui B, Bricca G, Lantelme P. Baroreceptor stimulation for resistant hypertension: first implantation in France and literature review. Arch Cardiovasc Dis. 2014;107:690–6. - PubMed
  21. Griffith LS, Schwartz SI. Reversal of renal hypertension by electrical stimulation of the carotid sinus nerve. Surgery. 1964;56:232–9. - PubMed
  22. Lohmeier TE, Barrett AM, Irwin ED. Prolonged activation of the baroreflex: a viable approach for the treatment of hypertension? Curr Hypertens Rep. 2005;7:193–8. - PubMed
  23. Matsukawa T, Gotoh E, Hasegawa O, Shionoiri H, Tochikubo O, Ishii M. Reduced baroreflex changes in muscle sympathetic nerve activity during blood pressure elevation in essential hypertension. J Hypertens. 1991;9:537–42. - PubMed
  24. Schiffrin EL. Reactivity of small blood vessels in hypertension: relation with structural changes. State of the art lecture. Hypertension. 1992;19:II1–9. - PubMed
  25. Naito Y, Yoshida H, Konishi C, Ohara N. Differences in responses to norepinephrine and adenosine triphosphate in isolated, perfused mesenteric vascular beds between normotensive and spontaneously hypertensive rats. J Cardiovasc Pharmacol. 1998;32:807–18. - PubMed
  26. Versari D, Daghini E, Virdis A, Ghiadoni L, Taddei S. Endothelium-dependent contractions and endothelial dysfunction in human hypertension. Br J Pharmacol. 2009;157:527–36. - PubMed
  27. Luscher TF, Vanhoutte PM. Endothelium-dependent contractions to acetylcholine in the aorta of the spontaneously hypertensive rat. Hypertension. 1986;8:344–8. - PubMed
  28. Linder L, Kiowski W, Buhler FR, Luscher TF. Indirect evidence for release of endothelium-derived relaxing factor in human forearm circulation in vivo. Blunted response in essential hypertension. Circulation. 1990;81:1762–7. - PubMed
  29. Taddei S, Virdis A, Mattei P, Salvetti A. Vasodilation to acetylcholine in primary and secondary forms of human hypertension. Hypertension. 1993;21:929–33. - PubMed
  30. Armario P, Oliveras A, Hernandez Del Rey R, Ruilope LM, De La Sierra A, Grupo de Investigadores del Registro de Hipertension refractaria de la Sociedad Espanola de Hipertension/Liga Espanola para la Lucha contra la Hipertension, Arterial. [Prevalence of target organ damage and metabolic abnormalities in resistant hypertension]. Med Clin. 2011;137:435–9. - PubMed
  31. Friberg P, Karlsson B, Nordlander M. Sympathetic and parasympathetic influence on blood pressure and heart rate variability in Wistar-Kyoto and spontaneously hypertensive rats. J Hypertens Suppl. 1988;6:S58–60. - PubMed
  32. Ricksten SE, Lundin S, Thoren P. Spontaneous variations in arterial blood pressure, heart rate and sympathetic nerve activity in conscious normotensive and spontaneously hypertensive rats. Acta Physiol Scand. 1984;120:595–600. - PubMed
  33. Pagani M, Lombardi F, Guzzetti S, Rimoldi O, Furlan R, Pizzinelli P, et al. Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho-vagal interaction in man and conscious dog. Circ Res. 1986;59:178–93. - PubMed
  34. Pomeranz B, Macaulay RJ, Caudill MA, Kutz I, Adam D, Gordon D, et al. Assessment of autonomic function in humans by heart rate spectral analysis. Am J Physiol. 1985;248:H151–3. - PubMed
  35. Liao D, Cai J, Barnes RW, Tyroler HA, Rautaharju P, Holme I, et al. Association of cardiac automatic function and the development of hypertension: the ARIC study. Am J Hypertens. 1996;9:1147–56. - PubMed
  36. Fagard RH, Pardaens K, Staessen JA. Relationships of heart rate and heart rate variability with conventional and ambulatory blood pressure in the population. J Hypertens. 2001;19:389–97. - PubMed
  37. Lucini D, Mela GS, Malliani A, Pagani M. Impairment in cardiac autonomic regulation preceding arterial hypertension in humans. Circulation. 2002;106:2673–9. - PubMed
  38. Silva LEV, Geraldini VR, de Oliveira BP, Silva CAA, Porta A, Fazan R. Comparison between spectral analysis and symbolic dynamics for heart rate variability analysis in the rat. Sci Rep. 2017;7:8428. - PubMed
  39. Margatho LO, Porcari CY, Macchione AF, da Silva Souza GD, Caeiro XE, Antunes-Rodrigues J, et al. Temporal dissociation between sodium depletion and sodium appetite appearance: involvement of inhibitory and stimulatory signals. Neuroscience. 2015;297:78–88. - PubMed
  40. Domingos-Souza G, Meschiari CA, Buzelle SL, Callera JC, Antunes-Rodrigues J. Sodium and water intake are not affected by GABAC receptor activation in the lateral parabrachial nucleus of sodium-depleted rats. J Chem Neuroanat. 2016;74:47–54. - PubMed
  41. Katayama PL, Castania JA, Dias DP, Patel KP, Fazan R Jr, Salgado HC. Role of chemoreceptor activation in hemodynamic responses to electrical stimulation of the carotid sinus in conscious rats. Hypertension. 2015;66:598–603. - PubMed
  42. Domingos-Souza G, Santos-Almeida FM, Meschiari CA, Ferreira NS, Pereira CA, Martinez D, et al. Electrical stimulation of the carotid sinus lowers arterial pressure and improves heart rate variability in L-NAME hypertensive conscious rats. Hypertens Res. 2020. https://doi.org/10.1038/s41440-020-0448-7 . - PubMed
  43. Santos-Almeida FM, Domingos-Souza G, Meschiari CA, Favaro LC, Becari C, Castania JA, et al. Carotid sinus nerve electrical stimulation in conscious rats attenuates systemic inflammation via chemoreceptor activation. Sci Rep. 2017;7:6265. - PubMed
  44. Domingos-Souza GS, Santos-Almeida FM, Silva LE, Dias D, Silva CA, Castania JA, et al. Electrical stimulation of carotid sinus in conscious normotensive and spontaneously hypertensive rats. FASEB J. 2015;29. https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fasebj.29.1_supplement.648.10 . - PubMed
  45. Tremoleda JL, Kerton A, Gsell W. Anaesthesia and physiological monitoring during in vivo imaging of laboratory rodents: considerations on experimental outcomes and animal welfare. EJNMMI Res. 2012;2:44. - PubMed
  46. Albrecht M, Henke J, Tacke S, Markert M, Guth B. Effects of isoflurane, ketamine-xylazine and a combination of medetomidine, midazolam and fentanyl on physiological variables continuously measured by telemetry in Wistar rats. BMC Vet Res. 2014;10:198. https://doi.org/10.1186/s12917-014-0198-3 . - PubMed
  47. Janssen BJA, De Celle T, Debets JJM, Brouns AE, Callahan MF, Smith TL. Effects of anesthetics on systemic hemodynamics in mice. Am J Physiol Heart Circ Physiol. 2004;287:H1618–24. - PubMed
  48. Heusser K, Tank J, Luft FC, Jordan J. Baroreflex failure. Hypertension. 2005;45:834–9. - PubMed
  49. Robertson D, Hollister AS, Biaggioni I, Netterville JL, Mosqueda-Garcia R, Robertson RM. The diagnosis and treatment of baroreflex failure. N. Engl J Med. 1993;329:1449–55. - PubMed
  50. van de Borne P, Montano N, Pagani M, Oren R, Somers VK. Absence of low-frequency variability of sympathetic nerve activity in severe heart failure. Circulation. 1997;95:1449–54. - PubMed
  51. Montano N, Ruscone TG, Porta A, Lombardi F, Pagani M, Malliani A. Power spectrum analysis of heart rate variability to assess the changes in sympathovagal balance during graded orthostatic tilt. Circulation. 1994;90:1826–31. - PubMed
  52. Billman GE. Heart rate variability - a historical perspective. Front Physiol. 2011;2:86. - PubMed
  53. Duque JJ, Silva LE, Murta LO. Open architecture software platform for biomedical signal analysis. Annu Int Conf IEEE Eng Med Biol Soc. 2013;2013:2084–7. - PubMed
  54. Di Rienzo M, Parati G, Castiglioni P, Tordi R, Mancia G, Pedotti A. Baroreflex effectiveness index: an additional measure of baroreflex control of heart rate in daily life. Am J Physiol Regul Integr Comp Physiol. 2001;280:R744–51. - PubMed
  55. Scheffers IJ, Kroon AA, Schmidli J, Jordan J, Tordoir JJ, Mohaupt MG, et al. Novel baroreflex activation therapy in resistant hypertension: results of a European multi-center feasibility study. J Am Coll Cardiol. 2010;56:1254–8. - PubMed
  56. Wallbach M, Lehnig L-Y, Schroer C, Lüders S, Böhning E, Müller GA, et al. Effects of baroreflex activation therapy on ambulatory blood pressure in patients with resistant hypertension. Hypertension. 2016;67:701–9. - PubMed
  57. Iliescu R, Tudorancea I, Lohmeier TE. Baroreflex activation: from mechanisms to therapy for cardiovascular disease. Curr Hypertens Rep. 2014;16:453. - PubMed
  58. Lohmeier TE, Iliescu R, Dwyer TM, Irwin ED, Cates AW, Rossing MA. Sustained suppression of sympathetic activity and arterial pressure during chronic activation of the carotid baroreflex. Am J Physiol Heart Circ Physiol. 2010;299:H402–9. - PubMed
  59. Tohyama T, Hosokawa K, Saku K, Oga Y, Tsutsui H, Sunagawa K. Smart baroreceptor activation therapy strikingly attenuates blood pressure variability in hypertensive rats with impaired baroreceptor. Hypertension. 2020;75:885–92. - PubMed
  60. Charkoudian N, Joyner MJ, Sokolnicki LA, Johnson CP, Eisenach JH, Dietz NM, et al. Vascular adrenergic responsiveness is inversely related to tonic activity of sympathetic vasoconstrictor nerves in humans. J Physiol. 2006;572:821–7. - PubMed
  61. Yeoh M, McLachlan EM, Brock JA. Tail arteries from chronically spinalized rats have potentiated responses to nerve stimulation in vitro. J Physiol. 2004;556:545–55. - PubMed
  62. Lee J-S, Fang S-Y, Roan J-N, Jou I-M, Lam C-F. Spinal cord injury enhances arterial expression and reactivity of α1-adrenergic receptors-mechanistic investigation into autonomic dysreflexia. Spine J. 2016;16:65–71. - PubMed

Publication Types