Chronic cholinergic stimulation promotes changes in cardiovascular autonomic control in spontaneously hypertensive rats

Blanco, João Henrique Dutra; Gastaldi, Ada Clarice; Gardim, Camila Balsamo; Araújo, João Luiz Vitorino; Simões, Marcus Vinı́cius; Oliveira, Luciano Fonseca Lemos de; Carvalho, Eduardo Elias Vieira de; Souza, Hugo Celso Dutra de

doi:10.1016/j.autneu.2015.09.002

Cited by 23 publications

(19 citation statements)

References 35 publications

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“…The cholinergic muscarinic 2 receptor (CHRM2) is a cholinergic neurotransmitter, and cholinergic stimulation through inhibition of the release of acetylcholinesterase has been shown to have a role in autonomic cardiac control 32 . In our study, propofol produced a significantly less change in HR in the 34.56% (47/136) of homozygous carriers of the major allele (CC) of rs2283265 in CHRM2, compared to the 65.44% (89/136) of patients who were heterozygous or homozygous for the minor allele (CA + AA) (−8.25% ± 7.15 mmHg vs. −10.86% ± 7.32, P = 0.048, df = 1, F = 3.965).…”

Section: Resultsmentioning

confidence: 99%

“…The CHRM2 receptor is a cholinergic neurotransmitter, and cholinergic stimulation via the inhibition of acetylcholinesterase release has demonstrated the role of the cholinergic system in autonomic cardiac control 32 . Evidence from animal models and clinical trials suggests that modulating cholinergic activity and restoring sympathovagal balance has salutary effects on hemodynamics 57 .…”

Section: Discussionmentioning

confidence: 99%

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Association of Polymorphisms in Pharmacogenetic Candidate Genes with Propofol Susceptibility

Zhong

Chen

Zhao

et al. 2017

Sci Rep

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Significant individual susceptibility to intravenous anesthetic propofol exists. The etiology of individual variability in the response to propofol may be influenced by genetic polymorphisms in metabolic and functional pathways. With current pharmacogenetics and modern molecular biology technologies, it is possible to study the influence of genetic polymorphisms on susceptibility to propofol. When inducing general anesthesia with intravenous propofol, high individual susceptibility to propofol was found. Using Sequenom MassARRAY single-nucleotide polymorphism (SNP) genotyping, we identified a mutation (rs6313) in the 5HT2A gene that was correlated to individual susceptibility to propofol effect-site concentration (Cep) and onset time of propofol induction. Carriers of the minor allele (G) of 5HT2A rs6313 required less propofol (20% decrease in Cep) and less time (40% decrease in onset time) to induce anesthesia. Moreover, associations were found between the gamma-aminobutyric acid (GABA) receptor SNP rs2279020 and the SCN9A SNP rs6746030 and the susceptibility of bispectral index (BIS) after propofol-induced anesthesia. In addition, dominant mutations in GABAA1 rs2279020, GABAA2 rs11503014, and CHRM2 rs1824024 were putatively associated with cardiovascular susceptibility to propofol anesthesia. No gene-gene interactions were found through a standardized measure of linkage disequilibrium and a multifactor dimensionality reduction analysis. Our results suggest that genetic polymorphisms related to mechanisms of propofol anesthesia are involved in propofol susceptibility.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Association of Polymorphisms in Pharmacogenetic Candidate Genes with Propofol Susceptibility

Zhong

Chen

Zhao

et al. 2017

Sci Rep

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“…In SHRs, augmented angiotensinogen and AT 1 receptor expression levels are also accompanied by a high level of oxidative stress and increased synthesis of proinflammatory cytokines in the PVN, NTS, and RVLM (116,158,182). These changes are associated with impaired baroreceptor reflex control, increased blood pressure fluctuation, and reduced heart rate variability (73,130), resulting in increased sympathetic outflow to the heart and blood vessels and reduced parasympathetic modulation of the heart in SHRs (10,117). Increased blood-brain barrier (BBB) perme-ability may be another mechanism contributing to autonomic dysfunction in hypertension (9).…”

Section: Effects Of Exercise Training On the Pvn And Autonomic Control In Hypertensionmentioning

confidence: 99%

Regulation of sympathetic vasomotor activity by the hypothalamic paraventricular nucleus in normotensive and hypertensive states

Dampney

Michelini

et al. 2018

American Journal of Physiology-Heart and Circulatory Physiology

116

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The hypothalamic paraventricular nucleus (PVN) is a unique and important brain region involved in the control of cardiovascular, neuroendocrine, and other physiological functions pertinent to homeostasis. The PVN is a major source of excitatory drive to the spinal sympathetic outflow via both direct and indirect projections. In this review, we discuss the role of the PVN in the regulation of sympathetic output in normal physiological conditions and in hypertension. In normal healthy animals, the PVN presympathetic neurons do not appear to have a major role in sustaining resting sympathetic vasomotor activity or in regulating sympathetic responses to short-term homeostatic challenges such as acute hypotension or hypoxia. Their role is, however, much more significant during longer-term challenges, such as sustained water deprivation, chronic intermittent hypoxia and pregnancy. The PVN also appears to have a major role in generating the increased sympathetic vasomotor activity that is characteristic of multiple forms of hypertension. Recent studies in the spontaneously hypertensive rat (SHR) model show that impaired inhibitory and enhanced excitatory synaptic inputs to PVN presympathetic neurons are the basis for heightened sympathetic outflow in hypertension. We discuss the molecular mechanisms underlying the presynaptic and postsynaptic alterations in GABAergic and glutamatergic inputs to PVN presympathetic neurons in hypertension. In addition, we discuss the ability of exercise training to correct sympathetic hyperactivity by restoring blood-brain barrier integrity, reducing angiotensin II availability, and decreasing oxidative stress and inflammation in the PVN.

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“…The spontaneously hypertensive rat (SHR) have been used as an important tool to understanding cardiovascular dysfunctions, such as high blood pressure (BP), endothelial injury and abnormal neural control of the cardiovascular system (Vasquez et al, 1997 ; Abreu et al, 1998 ; Blanco et al, 2015 ; Friques et al, 2015 ). In recent years, this hypertensive animal emerged as a promising model to identify alternative or non-pharmacological agents for prevention/treatment of cardiovascular disease because it develops essential hypertension (Ceroni et al, 2009 ; Monteiro et al, 2012 ; Barbosa Neto et al, 2013 ; Friques et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Effects of Kefir on the Cardiac Autonomic Tones and Baroreflex Sensitivity in Spontaneously Hypertensive Rats

et al. 2016

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Aims: It has been previously shown that the probiotic kefir (a symbiotic matrix containing acid bacteria and yeasts) attenuated the hypertension and the endothelial dysfunction in spontaneously hypertensive rats (SHR). In the present study, the effect of chronic administration of kefir on the cardiac autonomic control of heart rate (HR) and baroreflex sensitivity (BRS) in SHR was evaluated.Methods: SHR were treated with kefir (0.3 mL/100 g body weight) for 60 days and compared with non-treated SHR and with normotensive Wistar-Kyoto rats. Cardiac autonomic vagal (VT) and sympathetic (ST) tones were estimated through the blockade of the cardiac muscarinic receptors (methylatropine) and the blockade of β1−adrenoceptor (atenolol). The BRS was evaluated by the tachycardia and bradycardia responses to vasoactive drug-induced decreases and increases in arterial blood pressure (BP), respectively. Additionally, spontaneous BRS was estimated by autoregressive spectral analysis.Results: Kefir-treated SHR exhibited significant attenuation of basal BP, HR, and cardiac hypertrophy compared to non-treated SHR (12, 13, and 21%, respectively). Cardiac VT and ST were significantly altered in the SHR (~40 and ~90 bpm) compared with Wistar rats (~120 and ~30 bpm) and were partially recovered in SHR-kefir (~90 and ~25 bpm). SHR exhibited an impaired bradycardic BRS (~50%) compared with Wistar rats, which was reduced to ~40% in the kefir-treated SHR and abolished by methylatropine in all groups. SHR also exhibited a significant impairment of the tachycardic BRS (~23%) compared with Wistar rats and this difference was reduced to 8% in the SHR-kefir. Under the action of atenolol the residual reflex tachycardia was smaller in SHR than in Wistar rats and kefir attenuated this abnormality. Spectral analysis revealed increased low frequency components of BP (~3.5-fold) and pulse interval (~2-fold) compared with Wistar rats and these differences were reduced by kefir-treatment to ~1.6- and ~1.5-fold, respectively. Spectral analysis also showed an impairment of spontaneous BRS in SHR, but kefir-treatment caused only a tendency to reverse this result.Conclusions: The novelty of this study is that daily chronic consumption of a low dose of kefir reduced the impairment of the cardiac autonomic control of HR and of the impaired BRS in SHR.

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Chronic cholinergic stimulation promotes changes in cardiovascular autonomic control in spontaneously hypertensive rats

Cited by 23 publications

References 35 publications

Association of Polymorphisms in Pharmacogenetic Candidate Genes with Propofol Susceptibility

Association of Polymorphisms in Pharmacogenetic Candidate Genes with Propofol Susceptibility

Regulation of sympathetic vasomotor activity by the hypothalamic paraventricular nucleus in normotensive and hypertensive states

Effects of Kefir on the Cardiac Autonomic Tones and Baroreflex Sensitivity in Spontaneously Hypertensive Rats

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