Effects of carvedilol on M2 receptors and cholinesterase-positive nerves in adriamycin-induced rat failing heart

Xu, Xinyun; Zang, Wei-Jin; Lu, Jun; Kang, X.; Li, Ming; Yu, Xin

doi:10.1016/j.autneu.2006.04.005

Cited by 22 publications

(18 citation statements)

References 48 publications

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“…Concerning parasympathetic modulation, reduced nHF in DOX group, detected in our study, could be further interpreted as a consequence of a decreased expression of M2 receptors in cardiomyocytes of DOX-treated rats [70] in accordance with the study of Ribeiro et al [71], who showed that M2 receptor level was significantly correlated with HF power values in the human heart.…”

Section: Discussionsupporting

confidence: 91%

Cardiac autonomic modulation induced by doxorubicin in a rodent model of colorectal cancer and the influence of fullerenol pretreatment

et al. 2017

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The very effective anticancer drug doxorubicin (DOX) is known to have cardiotoxic side effects, which could be accompanied by autonomic modulation. Autonomic disbalance might even be an initiating mechanism underlying DOX-induced cardiotoxicity and can be studied noninvasively by the analysis of heart rate variability (HRV). A number of strategies have been assessed to predict chemotherapy-induced cardiac dysfunction while HRV, a potential detecting tool, has not yet been tested. Thus, we aimed to determine the effect of DOX treatment on HRV in a rat model of colorectal cancer. While pretreatment with fullerenol (Frl) acts protectively on DOX-induced cardiotoxicity, we aimed to test the effect of Frl pretreatment on DOX-induced HRV alterations. After the induction of colorectal cancer, adult male Wistar rats were treated with saline (n = 7), DOX (1.5 mg/kg per week, n = 7) or DOX after pretreatment with Frl (25 mg/kg per week, n = 7) for three weeks (cumulative DOX dose 4.5 mg/kg). One week after treatment rats were anaesthetized, standard ECG was measured and HRV was analyzed in time and frequency domain. During autopsy the intestines and hearts were gathered for biochemical analysis and histopathological examination. DOX treatment significantly decreased parasympathetically mediated high-frequency component (p<0.05) and increased the low-frequency component of HRV (p<0.05), resulting in an increased LF/HF ratio (p<0.05) in cancerous rats. When pretreated with Frl, DOX-induced HRV alterations were prevented: the high-frequency component of HRV increased (p<0.01), the low-frequency decreased (p<0.01), LF/HF ratio decreased consequently (p<0.01) compared to DOX only treatment. In all DOX-treated animals, disbalance of oxidative status in heart tissue and early myocardial lesions were found and were significantly reduced in rats receiving Frl pretreatment. Autonomic modulation accompanied the development of DOX-induced cardiotoxicity in rat model of colorectal cancer and was prevented by Frl pretreatment. Our results demonstrated the positive prognostic power of HRV for the early detection of DOX-induced cardiotoxicity.

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Section: Discussionsupporting

confidence: 91%

Cardiac autonomic modulation induced by doxorubicin in a rodent model of colorectal cancer and the influence of fullerenol pretreatment

et al. 2017

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“…Co-localization of ACh-related proteins in nerve Wbers and neurons can substitute for the cholinergic phenotype. We have shown previously that cholinesterase-positive nerves and M 2 receptors expression are down-regulated in rats with heart failure (Xu et al 2006). The present study further shows that down-regulation of cholinesterasepositive nerves and M 2 receptors expression in the left ventricular wall is observed in the hyperlipidemic state.…”

Section: Hyperlipidemia Avects the Expression Of Cholinesterase-positsupporting

confidence: 84%

Exercise benefits cardiovascular health in hyperlipidemia rats correlating with changes of the cardiac vagus nerve

et al. 2009

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The role of exercise training on hemodynamic parameters, blood lipid profiles, inflammatory cytokines, cholinesterase-positive nerves and muscarinic cholinergic (M(2)) receptors expression in the heart was investigated in Sprague-Dawley male rats with hyperlipidemia (HL). The rats were subjected to a high-fat diet and exercise training for 8 weeks, and then the hemodynamic parameters, the profiles of blood lipid and inflammatory cytokines, and the expression of cholinesterase-positive nerves and M(2) receptors were measured. HL rats displayed cardiac dysfunction, dysregulation of inflammatory cytokines, and decreased cholinesterase-positive nerves and M(2) receptors expression. The combination of hyperlipidemia with exercise training (AT) restored the profiles of blood lipids and the levels of inflammatory cytokines. In addition, AT and HL + AT improved cardiac function with increasing cholinesterase-positive nerves and M(2) receptors expression. Overall, these data show that the increased expression of cholinesterase-positive nerves and M(2) receptors in the heart is partially responsible for the benefits of exercise training on cardiac function in hyperlipidemia rats.

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“…Indeed, in a previous study we showed that decreased NGF transcripts in CG neurons after cardiac sympathectomy correlated with similar declines in NGFβ protein, whereas proNGF expression remained stable (Hasan et al, 2009). Although we have not examined atrial innervation in this study, decreases in parasympathetic markers, and increases in sympathetic markers, have been reported by others (Lund et al, 1983; Ng et al, 2011; Roskoski et al, 1975; Xu et al, 2006). However, depending on the model, regional variations in innervation patterns are observed for both sympathetic and parasympathetic fibers.…”

Section: Discussionmentioning

confidence: 63%

Decreased adrenoceptor stimulation in heart failure rats reduces NGF expression by cardiac parasympathetic neurons

Hasan

Smith

2014

Autonomic Neuroscience

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Postganglionic cardiac parasympathetic and sympathetic nerves are physically proximate in atrial cardiac tissue allowing reciprocal inhibition of neurotransmitter release, depending on demands from central cardiovascular centers or reflex pathways. Parasympathetic cardiac ganglion (CG) neurons synthesize and release the sympathetic neurotrophin nerve growth factor (NGF), which may serve to maintain these close connections. In this study we investigated whether NGF synthesis by CG neurons is altered in heart failure, and whether norepinephrine from sympathetic neurons promotes NGF synthesis. NGF and proNGF immunoreactivity in CG neurons in heart failure rats following chronic coronary artery ligation was investigated. NGF immunoreactivity was decreased significantly in heart failure rats compared to sham-operated animals, whereas proNGF expression was unchanged. Changes in neurochemistry of CG neurons included attenuated expression of the cholinergic marker vesicular acetylcholine transporter, and increased expression of the neuropeptide vasoactive intestinal polypeptide. To further investigate norepinephrine’s role in promoting NGF synthesis, we cultured CG neurons treated with adrenergic receptor (AR) agonists. An 82% increase in NGF mRNA levels was detected after 1hr of isoproterenol (β-AR agonist) treatment, which increased an additional 22% at 24hr. Antagonist treatment blocked isoproterenol-induced increases in NGF transcripts. In contrast, the α-AR agonist phenylephrine did not alter NGF mRNA expression. These results are consistent with β-AR mediated maintenance of NGF synthesis in CG neurons. In heart failure, a decrease in NGF synthesis by CG neurons may potentially contribute to reduced connections with adjacent sympathetic nerves.

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Effects of carvedilol on M2 receptors and cholinesterase-positive nerves in adriamycin-induced rat failing heart

Cited by 22 publications

References 48 publications

Cardiac autonomic modulation induced by doxorubicin in a rodent model of colorectal cancer and the influence of fullerenol pretreatment

Cardiac autonomic modulation induced by doxorubicin in a rodent model of colorectal cancer and the influence of fullerenol pretreatment

Exercise benefits cardiovascular health in hyperlipidemia rats correlating with changes of the cardiac vagus nerve

Decreased adrenoceptor stimulation in heart failure rats reduces NGF expression by cardiac parasympathetic neurons

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