Author + information
- Lijun Cheng,
- Guangping Li,
- Jian Li and
- Xinghua Wang
Heart disease will lead to sympathetic nerve remodeling. These sympathetic nerves include the sympathetic nerve in the heart, as well as the distal sympathetic nerve innervating the heart, such as sympathetic ganglion. Superior cervical ganglion (SCG) plays an important role in cardiovascular diseases. The electrical activity of SCG neurons is involved in the regulation of the autonomic nervous system. The aim of this research is to evaluate the effects of Fluvastatin on cardiac sympathetic nerve remodeling and the electrophysiological characteristics of SCG neurons in myocardial ischemia (MI).
The MI in rabbit model was induced by abdominal subcutaneous injections of isoproterenol (ISO). With whole-cell patch-clamp technique, we studied the characteristic change of ion channels (including sodium channel and delayed rectifier potassium channel) and action potentials (AP) on isolated SCG neurons in control group, MI group (85mg/kg/day, twice at an interval of 24 hours) and Fluvastatin (10mg/kg/d, 7 days) pre-treated group (Fluvastatin group) respectively. The expression level of tyrosine hydroxylase (TH) and growth associated protein 43 (GAP43) in ventricular muscle tissue and SCG tissue were determined by immunohistochemistry. Results were expressed as mean S.D. The comparison between two groups was used t-test and the comparison between three groups was used one-way analysis of variance (ANOVA). P<0.05 was considered to be statistical difference.
1. The maximal peak current density of delayed rectifier potassium channels of rabbits SCG neurons was (80.80±22.80) pA/pF, (154.93±31.56) pA/pF and (119.82±24.82) pA/pF in control group, MI group and Fluvastatin group respectively (n=10, P<0.05). The amplitude of delayed rectifier potassium channel current of SCG neurons was increased in MI (P<0.05), which was reduced by Fluvastatin. Furthermore, the activation curve in control group, MI group and Fluvastatin group (n=10) was found no significant difference (P>0.05).
2. The maximal peak current density of sodium channels on rabbits SCG neurons in control group, MI group and Fluvastatin group were (-102.71±9.55) pA/pF, (-154.41±23.64) pA/pF and (-116.28±30.23) pA/pF respectively (n=10, P<0.05). The characteristics of activation curves, inactivation curves and recovery curves after inactivation were changed in MI group (P<0.05). The intervention of Fluvastatin can mostly decrease the current amplitude which has been increased in MI, and move the activation curves and recovery curves after inactivation of Fluvastatin group in the direction of control group.
3. Resting potential of control group, MI group and Fluvastatin group were (-61.10±6.52) mV, (-67.25±7.19) mV and (-63.50±7.31) mV (n=8, P>0.05) respectively, there was no significant difference. The amplitude of AP in three group were (88.00±10.58) mV, (107.40±12.36) mV and (93.86±14.29) mV (n=8, P>0.05) respectively. The probability induced continuous AP (the number of neurons induced continuous AP / the total number of neurons recorded correct AP) were 50.00%, 14.29% and 33.33% respectively. MI reduced electrical activity of AP and increased amplitude of AP, and Fluvastatin pretreatment recovered amplitude and electrical activity of AP.
4. The expression level of TH and GAP43 of ventricular muscle tissue and SCG tissue in control group, MI group and Fluvastatin group was found no significant difference (n=5, P>0.05). The ratio of TH and GAP43 was found significant difference (P<0.05). Compared with the control group, the expression level of TH were decreased (P>0.05), while GAP43 was increased in ventricular muscle tissue and SCG tissue of MI group (P>0.05). the ratio of TH and GAP43 was decreased (P<0.05). And the changes were reversed by Fluvastatin treatment.
Fluvastatin pretreatment can recover sympathetic nerve remodeling on ventricular muscle tissue and SCG tissue as well as electrophysiological characteristics on SCG neurons in MI. It could be one of the potential mechanisms of statins in treating heart diseases.