Effects of rat sinoaortic denervation on the vagal responsiveness and expression of muscarinic acetylcholine receptors

Effects of rat sinoaortic denervation on the vagal responsiveness and expression of muscarinic acetylcholine receptors

Author Soares, PPD Google Scholar
Porto, Catarina Segreti Autor UNIFESP Google Scholar
Francis, F. M. Google Scholar
Abdalla, Fernando Mauricio Francis Autor UNIFESP Google Scholar
De La Fuente, R. N. Google Scholar
Moreira, E. D. Google Scholar
Krieger, E. M. Google Scholar
Irigoyen, Maria Claudia Autor UNIFESP Google Scholar
Institution Universidade Federal Fluminense (UFF)
Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Inst Butantan
Abstract We Studied heart rate (HR) responses to vagal electrical stimulation (VES) and the expression of muscarinic acetylcholine receptors (mAChRs) in the rat atria I day (SADa) and 20 days (SADc) after sinoaortic denervation (SAD). Arterial blood pressure (BP) was recorded in conscious. unrestrained rats and during vagal electrical stimulation of the vagus nerve. In the acute phase, SADa rats had hypertension, tachycardia, and increased blood pressure lability. In the chronic phase, heart rate and blood pressure in SADc rats returned to normal whereas blood pressure lability remained increased. VIES produced a frequency-dependent bradycardia that was higher in SADa and SADc groups. Binding experiments with [H-3] N-methylscopolamine showed that in the chronic phase of SAD mAChRs density (SADc = 412.2 +/- 28.64, SADa = 273.38 +/- 48.37 and CTR = 241.5 +/- 25.35 fmol/mg of protein, P < 0.05) and affinity increased in SADc rats (reduced dissociation constant: SADc = 0.45 +/- 0.05, SADa = 1.01 +/- 0.26, and CTR = 0.98 +/- 0.12 mM, P < 0.05). Our study provides evidence that vagal hyperresponsiveness coexists with increased sympathetic activity in SADa rats without a concomitant increase in mAChRs density or affinity, Suggesting that complex mechanisms might modulate the accentuated antagonism observed in the acute SAD phase. However, SADc rats had increased bradycardia to VES, increased affinity, and upregulation of mAChRs in the atria. Our results show that, 20 days after SAD in the rat, functional and cellular adaptations occur in the cardiac parasympathetic efferent pathway that may contribute to other regulatory mechanisms to compensate for cardiovascular changes provoked by baroreceptor arch disruption.
Keywords baroreflex
muscarinic receptors
sinoaortic denervation
vagal stimulation
Language English
Date 2006-03-01
Published in Journal Of Cardiovascular Pharmacology. Philadelphia: Lippincott Williams & Wilkins, v. 47, n. 3, p. 331-336, 2006.
ISSN 0160-2446 (Sherpa/Romeo, impact factor)
Publisher Lippincott Williams & Wilkins
Extent 331-336
Origin http://dx.doi.org/10.1097/01.fjc.0000205982.67653.26
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000236719600002
URI http://repositorio.unifesp.br/11600/44218

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