Acetylcholinesterase Inhibition Attenuates the Development of Hypertension and Inflammation in Spontaneously Hypertensive Rats

Lataro, Renata Maria; Silva, Carlos A. A.; Tefé‐Silva, Cristiane; Prado, Cibele M.; Salgado, Hélio César

doi:10.1093/ajh/hpv017

Cited by 60 publications

(33 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, there was no significant difference in HR among groups in the present study. Some studies have revealed a pyridostigmine‐induced increase in HR after the removal of adrenergic and cholinergic influences on the heart by propranolol and methylatropine in models of sympathetic hyperactivity‐induced cardiac dysfunction . These data indicate that pyridostigmine itself may increase HR, which may counteract the reduction of HR induced by ACh.…”

Section: Discussionmentioning

confidence: 94%

Long‐term administration of pyridostigmine attenuates pressure overload‐induced cardiac hypertrophy by inhibiting calcineurin signalling

Lü

Zhao

Liu

et al. 2017

J Cellular Molecular Medi

View full text Add to dashboard Cite

Cardiac hypertrophy is associated with autonomic imbalance, characterized by enhanced sympathetic activity and withdrawal of parasympathetic control. Increased parasympathetic function improves ventricular performance. However, whether pyridostigmine, a reversible acetylcholinesterase inhibitor, can offset cardiac hypertrophy induced by pressure overload remains unclear. Hence, this study aimed to determine whether pyridostigmine can ameliorate pressure overload‐induced cardiac hypertrophy and identify the underlying mechanisms. Rats were subjected to either sham or constriction of abdominal aorta surgery and treated with or without pyridostigmine for 8 weeks. Vagal activity and cardiac function were determined using PowerLab. Cardiac hypertrophy was evaluated using various histological stains. Protein markers for cardiac hypertrophy were quantitated by Western blot and immunoprecipitation. Pressure overload resulted in a marked reduction in vagal discharge and a profound increase in cardiac hypertrophy index and cardiac dysfunction. Pyridostigmine increased the acetylcholine levels by inhibiting acetylcholinesterase in rats with pressure overload. Pyridostigmine significantly attenuated cardiac hypertrophy based on reduction in left ventricular weight/body weight, suppression of the levels of atrial natriuretic peptide, brain natriuretic peptide and β‐myosin heavy chain, and a reduction in cardiac fibrosis. These effects were accompanied by marked improvement of cardiac function. Additionally, pyridostigmine inhibited the CaN/NFAT3/GATA4 pathway and suppressed Orai1/STIM1 complex formation. In conclusion, pressure overload resulted in cardiac hypertrophy, cardiac dysfunction and a significant reduction in vagal discharge. Pyridostigmine attenuated cardiac hypertrophy and improved cardiac function, which was related to improved cholinergic transmission efficiency (decreased acetylcholinesterase and increased acetylcholine), inhibition of the CaN/NFAT3/GATA4 pathway and suppression of the interaction of Orai1/STIM1.

show abstract

Section: Discussionmentioning

confidence: 94%

Long‐term administration of pyridostigmine attenuates pressure overload‐induced cardiac hypertrophy by inhibiting calcineurin signalling

Lü

Zhao

Liu

et al. 2017

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…In addition, treatment with the peripherally-acting AChE inhibitor neostigmine fails to alleviate organ injury in murine endotoxemia [103] and pro-inflammatory cytokine responses associated with mechanical ventilation [104]. Very recently, treatment with the centrally-acting AChE inhibitor donepezil has been shown to increase vagal tone, suppress plasma TNF, IL-6 and IFN-γ levels, attenuate development of hypertension and prevent cardiac remodeling in spontaneously hypertensive rats [105]. In contrast, treatment with the peripherally-acting AChE inhibitor pyridostigmine fails to suppress plasma pro-inflammatory cytokine levels and reduce high blood pressure [105].…”

Section: The Remote Immunomodulatory Switches In the Brainmentioning

confidence: 99%

“…Very recently, treatment with the centrally-acting AChE inhibitor donepezil has been shown to increase vagal tone, suppress plasma TNF, IL-6 and IFN-γ levels, attenuate development of hypertension and prevent cardiac remodeling in spontaneously hypertensive rats [105]. In contrast, treatment with the peripherally-acting AChE inhibitor pyridostigmine fails to suppress plasma pro-inflammatory cytokine levels and reduce high blood pressure [105]. …”

Section: The Remote Immunomodulatory Switches In the Brainmentioning

confidence: 99%

Neural circuitry and immunity

2015

View full text Add to dashboard Cite

Research during the last decade has significantly advanced our understanding of the molecular mechanisms at the interface between the nervous system and the immune system. Insight into bidirectional neuroimmune communication has characterized the nervous system as an important partner of the immune system in the regulation of inflammation. Neuronal pathways, including the vagus nerve-based inflammatory reflex are physiological regulators of immune function and inflammation. In parallel, neuronal function is altered in conditions characterized by immune dysregulation and inflammation. Here, we review these regulatory mechanisms and describe the neural circuitry modulating immunity. Understanding these mechanisms reveals possibilities to use targeted neuromodulation as a therapeutic approach for inflammatory and autoimmune disorders. These findings and current clinical exploration of neuromodulation in the treatment of inflammatory diseases defines the emerging field of Bioelectronic Medicine.

show abstract

“…The released NO can diffuse into the tunica media and activate the soluble guanylate cyclase (sGC) in vascular smooth muscle cells to cause vasodilation [23,24]. ACh is one of neurotransmitters in the autonomic nervous system, acting through the muscarinic receptors, that induces vasodilation through conduction of the translocation of eNOS, which then increases the level of NO [25][26][27][28]. Therefore, chronic administration of L-NAME leads to a decrease in the ability of ACh to produce NO, which then reduces vasorelaxation.…”

Section: Discussionmentioning

confidence: 99%

Ethyl Rosmarinate Prevents the Impairment of Vascular Function and Morphological Changes in L-NAME-Induced Hypertensive Rats

et al. 2019

View full text Add to dashboard Cite

Background and Objectives: The potent, endothelium-independent, vasorelaxant effect of ethyl rosmarinate, an ester derivative of rosmarinic acid, makes it of interest as an alternative therapeutic agent for use in hypertension. This study was designed to investigate the effect of ethyl rosmarinate on N ω -nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. Materials and Methods: L-NAME was given orally to male Wistar rats for 6 weeks to induce hypertension concurrently with treatment of ethyl rosmarinate at 5, 15, or 30 mg/kgor enalapril at 10 mg/kg Systolic blood pressure (SBP), heart rate, and body weight of all experimental groups were recorded weekly, while the vascular sensitivity and histological changes of the aorta were evaluated at the end of the experiment. Results: For all treatment groups, the data indicated that ethyl rosmarinate significantly attenuated the SBP in hypertensive rats induced by L-NAME, with no significant differences in heart rate and body weight. In addition, the response of vascular sensitivity to acetylcholine (ACh) was improved but there was no significant difference in the response to sodium nitroprusside (SNP). Furthermore, the sensitivity of the aorta to phenylephrine (PE) was significantly decreased. The thickness of the aortic wall did not differ between groups but the expression of endothelial nitric oxide synthase (eNOS) was increased in ethyl rosmarinate-and enalapril-treated groups compared with the hypertensive group. Conclusions: Ethyl rosmarinate is an interesting candidate as an alternative treatment for hypertension due to its ability to improve vascular function and to increase the expression of eNOS similar to enalapril which is a drug commonly used in hypertension.

show abstract

Acetylcholinesterase Inhibition Attenuates the Development of Hypertension and Inflammation in Spontaneously Hypertensive Rats

Abstract: Donepezil attenuated the development of hypertension in SHR probably involving antiinflammatory effects, indicating that acetylcholinesterase inhibition yields benefic effects for antihypertensive therapy.

Cited by 60 publications

References 35 publications

Long‐term administration of pyridostigmine attenuates pressure overload‐induced cardiac hypertrophy by inhibiting calcineurin signalling

Long‐term administration of pyridostigmine attenuates pressure overload‐induced cardiac hypertrophy by inhibiting calcineurin signalling

Neural circuitry and immunity

Ethyl Rosmarinate Prevents the Impairment of Vascular Function and Morphological Changes in L-NAME-Induced Hypertensive Rats

Contact Info

Product

Resources

About