Cholinesterase inhibition prevents isoproterenol induced-hypertrophy.

<p><b>A.</b> Representative images. <b>B.</b> Morphometry analyses showing the increase in fiber diameter in rats subjected to seven day ISO administration. Cholinesterase inhibition prevented the ISO-induced cardiomyocyte hyperthophy. n = number of hearts analysed. *p<0.05 when compared to other groups. Scale bar = 10 µm.</p

Increased cholinergic signaling improves cardiac function in mice with sympathetic hyperactivity-induced heart failure.

<p><b>A–B</b>. Percentage increase in left ventricular ejection fraction and fractional shortening measured by echocardiography. Systolic tension (<b>C</b>) and cardiomyocyte shortening (<b>D</b>) measurements were performed in WT and α_2A/α_2C-KO mice treated or not with pyridostigmine. Cholinesterase inhibition therapy restored cardiac function and and cellular contractile function of α_2A/α_2C–KO mice to control levels. *p<0.05 when compared to WT and α_2A/α_2C–KO/PYR.</p

Echocardiographic parameters.

<p>Echocardiographic measurements of cardiac parameters in rats following isoproterenol injection for 7 days. Pyridostigmine treatment of ISO-rats attenuated the development of cardiac remodeling induced by isoproterenol. n = number of rats analysed in each experimental group.</p><p>* = p<0.05 versus CT,</p><p>& = p<0.05 versus ISO,</p><p># = p<0.05 versus ISO+PYR.</p

Opposite modulation of cardiomyocyte cholinergic machinery by isoproterenol and pyridostigmine.

<p><b>A–C</b>. qPCR experiments show that cardiomyocytes from ISO-rats present upregulation of VAChT, ChAT and M₂ muscarinic receptor mRNA levels. Cholinesterase inhibition prevented these effects. Lower levels of VAChT, ChAT and M₂ ACh muscarinic receptor transcripts were observed in cardiomyocytes from pyridostigmine treated rats. <b>D.</b> Downregulation of β1-AR transcript is observed in ventricular myocytes from ISO-rats, while pyridostigmine-treated rats presented opposite results. Cholinesterase therapy partially reversed the effect of ISO on β1-AR transcripts. n = 4–6 cardiomyocyte preparations from each group. *p<0.05 when compared to control group and #p<0.05 when compared to the ISO-treated rat.</p

Cholinesterase inhibition alters the activity of the cardiac autonomic system evoked by isoproterenol.

<p>Changes in heart rate (HR) under the inhibition of parasympathetic and/or sympathetic nervous system were monitored in rats injected with methylatropine and propranolol for further calculation of sympathetic and vagal tone, as described in Methods. Two different doses of pyridostigmine were combined with isoproterenol in this study (0.2 mg/kg body weight or 0.5 mg/kg body weight). <b>A–B.</b> ISO administration to rats for seven days resulted in increased sympathetic tone when compared with control group. Vagal tone was lower in isoproterenol treated rats when compared to control rats. The higher dose of pyridostigmine was more efficient in preventing the isoproterenol-induced changes in heart rate. Rats treated with pyridostigmine alone (0.5 mg/kg body weight) presented reduced sympathetic and increased parasympathetic tone, respectively. n = number of rats. *p<0.05 when compared to control group and #p<0.05 when compared to the ISO-treated rat using Student's <i>t</i> test.</p