Cellular and Molecular Neurobiology

, Volume 32, Issue 7, pp 1119–1126 | Cite as

Sudden Death and Myocardial Lesions after Damage to Catecholamine Neurons of the Nucleus Tractus Solitarii in Rat

  • William T. Talman
  • Deidre Nitschke Dragon
  • Susan Y. Jones
  • Steven A. Moore
  • Li-Hsien Lin
Original Research

Abstract

Lesions that remove neurons expressing neurokinin-1 (NK1) receptors from the nucleus tractus solitarii (NTS) without removing catecholaminergic neurons lead to loss of baroreflexes, labile arterial pressure, myocardial lesions, and sudden death. Because destruction of NTS catecholaminergic neurons expressing tyrosine hydroxylase (TH) may also cause lability of arterial pressure and loss of baroreflexes, we sought to test the hypothesis that cardiac lesions associated with lability are not dependent on damage to neurons with NK1 receptors but would also occur when TH neurons in NTS are targeted. To rid the NTS of TH neurons we microinjected anti-dopamine β-hydroxylase conjugated to saporin (anti-DBH-SAP, 42 ng/200 nl) into the NTS. After injection of the toxin unilaterally, immunofluorescent staining confirmed that anti-DBH-SAP decreased the number of neurons and fibers that contain TH and DBH in the injected side of the NTS while sparing neuronal elements expressing NK1 receptors. Bilateral injections in eight rats led to significant lability of arterial pressure. For example, on day 8 standard deviation of mean arterial pressure was 16.8 ± 2.5 mmHg when compared with a standard deviation of 7.83 ± 0.33 mmHg in six rats in which phosphate buffered saline (PBS) had been injected bilaterally. Two rats died suddenly at 5 and 8 days after anti-DBH-SAP injection. Seven-treated animals demonstrated microscopic myocardial necrosis as reported in animals with lesions of NTS neurons expressing NK1 receptors. Thus, cardiac and cardiovascular effects of lesions directed toward catecholamine neurons of the NTS are similar to those following damage directed toward NK1 receptor-containing neurons.

Keywords

Arrhythmia Baroreflex Catecholamine Lability Rat Saporin 

Notes

Acknowledgments

The study presented here was supported by National Institutes of Health RO1 HL 088090 (to L. H. Lin and W. T. Talman) and in part by a Department of Veterans Affairs Merit Review (to W. T. Talman). The authors gratefully acknowledge technical support provided by Dr. Wei Zhang in the initial microinjection studies and consultative support from Dr. Harald Stauss in sequence analysis of baroreflex function.

Conflict of interest

None of the authors has a real or perceived conflict of interest that could have, in any way, influenced the results or interpretation of the results of this study.

References

  1. Bertinieri G, di Rienzo M, Cavallazzi A, Ferrari AU, Pedotti A, Mancia G (1985) A new approach to analysis of the arterial baroreflex. J Hypertens Suppl 3:S79–S81PubMedGoogle Scholar
  2. Cowley AW, Liard JF, Guyton AC (1973) Role of the baroreceptor reflex in daily control of arterial blood pressure and other variables in dogs. Circ Res 32:564–576PubMedCrossRefGoogle Scholar
  3. di Rienzo M, Parati G, Castiglioni P, Tordi R, Mancia G, Pedotti A (2001) Baroreflex effectiveness index: an additional measure of baroreflex control of heart rate in daily life. Am J Physiol Regul Integr Comp Physiol 280:R744–R751PubMedGoogle Scholar
  4. Itoh H, Alper RH, Buñag RD (1992) Baroreflex changes produced by serotonergic or catecholaminergic lesions in the rat nucleus tractus solitarius. J Pharmacol Exp Ther 261:225–233PubMedGoogle Scholar
  5. Junqueira LF, Krieger EM (1976) Blood pressure and sleep in the rat in normotension and in neurogenic hypertension. J Physiol (London) 259:725–735Google Scholar
  6. Lin L-H, Talman WT (2006) Vesicular glutamate transporters and neuronal nitric oxide synthase colocalize in aortic depressor afferent neurons. J Chem Neuroanat 32:54–64PubMedCrossRefGoogle Scholar
  7. Lin LH, Taktakishvili O, Talman WT (2007) Identification and localization of cell types that express endothelial and neuronal nitric oxide synthase in the rat nucleus tractus solitarii. Brain Res 1171:42–51PubMedCrossRefGoogle Scholar
  8. Lin LH, Taktakishvili OM, Talman WT (2008) Colocalization of neurokinin-1,N-methyl-d-aspartate, and AMPA receptors on neurons of the rat nucleus tractus solitarii. Neuroscience 154:690–700PubMedCrossRefGoogle Scholar
  9. Lin L-H, Nitschke Dragon D, Talman WT (2012) Collateral damage and compensatory changes after injection of a toxin targeting neurons with the neurokinin-1 receptor in the nucleus tractus solitarii of rat. J Chem Neuroanat doi:10.1016/j.jchemneu.2012.02.001
  10. Madden CJ, Sved AF (2003) Cardiovascular regulation after destruction of the C1 cell group of the rostral ventrolateral medulla in rats. Am J Physiol Heart Circ Physiol 285:H2734–H2748PubMedGoogle Scholar
  11. Madden CJ, Ito S, Rinaman L, Wiley RG, Sved AF (1999) Lesions of the C1 catecholaminergic neurons of the ventrolateral medulla in rats using anti-DbetaH-saporin. Am J Physiol 277:R1063–R1075PubMedGoogle Scholar
  12. Massari VJ, Shirahata M, Johnson TA, Gatti PJ (1996) Carotid sinus nerve terminals which are tyrosine hydroxylase immunoreactive are found in the commissural nucleus of the tractus solitarius. J Neurocytol 25:197–208PubMedCrossRefGoogle Scholar
  13. Nathan MA, Reis DJ (1977) Chronic labile hypertension produced by lesions of the nucleus tractus solitarii in the cat. Circ Res 40:72–81PubMedCrossRefGoogle Scholar
  14. National Research Council (1996) Guide for the care and use of laboratory animals. National Academy Press, Washington, DCGoogle Scholar
  15. Nayate A, Moore SA, Weiss R, Taktakishvili O, Lin L-H, Talman WT (2008) Cardiac damage after lesions of the nucleus tractus solitarii. Am J Physiol Regul Integr Comp Physiol 296:R272–R279PubMedCrossRefGoogle Scholar
  16. Riley J, Lin L-H, Chianca DA Jr, Talman WT (2002) Ablation of NK1 receptors in rat nucleus tractus solitarii blocks baroreflexes. Hypertension 40:823–826PubMedCrossRefGoogle Scholar
  17. Rinaman L (2003) Hindbrain noradrenergic lesions attenuate anorexia and alter central cFos expression in rats after gastric viscerosensory stimulation. J Neurosci 23:10084–10092PubMedGoogle Scholar
  18. Snyder DW, Nathan MA, Reis DJ (1978) Chronic lability of arterial pressure produced by selective destruction of the catecholamine innervation of the nucleus tractus solitarii in the rat. Circ Res 43:662–671PubMedCrossRefGoogle Scholar
  19. Stauss H, Moffitt JA, Chapleau MW, Abboud FM, Johnson AK (2006) Baroreceptor reflex sensitivity estimated by the sequence technique is reliable in rats. Am J Physiol 291(1): H482–H483Google Scholar
  20. Talman WT, Kelkar P (1993) Neural control of the heart. Neurol Clin 11:239–255PubMedGoogle Scholar
  21. Talman WT, Snyder DW, Reis DJ (1980) Chronic lability of arterial pressure produced by destruction of A2 catecholaminergic neurons in rat brainstem. Circ Res 46:842–853PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC (outside the USA) 2012

Authors and Affiliations

  • William T. Talman
    • 1
  • Deidre Nitschke Dragon
    • 1
  • Susan Y. Jones
    • 1
  • Steven A. Moore
    • 2
  • Li-Hsien Lin
    • 1
  1. 1.Laboratory of Neurobiology, Department of NeurologyCarver College of Medicine, University of Iowa and Department of Veterans Affairs Medical CenterIowaUSA
  2. 2.Department of PathologyCarver College of Medicine, University of Iowa and Department of Veterans Affairs Medical CenterIowaUSA

Personalised recommendations