Yugen Shi1, Jie Yin1, Hesheng Hu1, Mei Xue1, Xiaolu Li1, Ju Liu2, Yan Li2, Wenjuan Cheng1, Ye Wang1, Xinran Li1, Yu Wang1, Fuhong Liu2, Qiang Liu2, Jiayu Tan1, Suhua Yan3. 1. Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Shandong, China. 2. Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Shandong, China. 3. Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Shandong, China. Electronic address: yansuhua296@163.com.
Abstract
BACKGROUND: The hypothalamic paraventricular nucleus (PVN) is the center of the regulation of autonomic nervous system functions and cardiovascular activity. Phosphoinositide-3 kinase (PI3K)-AKT pathway in PVN contributes to mediate sympathetic nerve activity and is activated in spontaneously hypertensive rats. Overactivation of the sympathetic output was considered as an important mechanism of the arrhythmias. In the present study, we aimed to explore whether targeted regulation of sympathetic activity in PVN could reduce the peripheral sympathoexcitatory and attenuate the ventricular arrhythmias (VAs) in myocardial infarction (MI) rats via PI3K-AKT pathway. METHODS: A stainless steel gauge guide cannula was stereotaxically implanted into the PVN, and 7 days later, rats were randomly divided into the following 4 groups: group A, control+dimethyl sulfoxide (DMSO); group B, control+LY294002; group C, MI surgery+DMSO; and group D, MI surgery+LY294002. Studies were conducted seven days post-MI. Myocardial function, infarct size, inducible VAs by programmed electrical stimulation, renal sympathetic nerve activity (RSNA), and protein level of PI3K and AKT were measured. RESULTS: MI increased the protein ratios of p-PI3K-to-total-PI3K and p-AKT-to-total-AKT in PVN but can be reduced by LY294002 treatment. Inhibition of sympathetic nerve activity in PVN led to a reversion in plasma norepinephrine, RSNA and inducible VAs in MI rats. CONCLUSIONS: PI3K-AKT pathway in the PVN was a main mechanism in regulating sympathetic activity and arrhythmias in MI rats. Targeted inhibition of sympathetic activity in PVN may be a potential treatment for the VAs via PI3K-AKT pathway.
BACKGROUND: The hypothalamic paraventricular nucleus (PVN) is the center of the regulation of autonomic nervous system functions and cardiovascular activity. Phosphoinositide-3 kinase (PI3K)-AKT pathway in PVN contributes to mediate sympathetic nerve activity and is activated in spontaneously hypertensiverats. Overactivation of the sympathetic output was considered as an important mechanism of the arrhythmias. In the present study, we aimed to explore whether targeted regulation of sympathetic activity in PVN could reduce the peripheral sympathoexcitatory and attenuate the ventricular arrhythmias (VAs) in myocardial infarction (MI) rats via PI3K-AKT pathway. METHODS: A stainless steel gauge guide cannula was stereotaxically implanted into the PVN, and 7 days later, rats were randomly divided into the following 4 groups: group A, control+dimethyl sulfoxide (DMSO); group B, control+LY294002; group C, MI surgery+DMSO; and group D, MI surgery+LY294002. Studies were conducted seven days post-MI. Myocardial function, infarct size, inducible VAs by programmed electrical stimulation, renal sympathetic nerve activity (RSNA), and protein level of PI3K and AKT were measured. RESULTS: MI increased the protein ratios of p-PI3K-to-total-PI3K and p-AKT-to-total-AKT in PVN but can be reduced by LY294002 treatment. Inhibition of sympathetic nerve activity in PVN led to a reversion in plasma norepinephrine, RSNA and inducible VAs in MI rats. CONCLUSIONS: PI3K-AKT pathway in the PVN was a main mechanism in regulating sympathetic activity and arrhythmias in MI rats. Targeted inhibition of sympathetic activity in PVN may be a potential treatment for the VAs via PI3K-AKT pathway.
Authors: Claudia Luna-Herrera; Irma A Martínez-Dávila; Luis O Soto-Rojas; Yazmin M Flores-Martinez; Manuel A Fernandez-Parrilla; Jose Ayala-Davila; Bertha A León-Chavez; Guadalupe Soto-Rodriguez; Victor M Blanco-Alvarez; Francisco E Lopez-Salas; Maria E Gutierrez-Castillo; Bismark Gatica-Garcia; America Padilla-Viveros; Cecilia Bañuelos; David Reyes-Corona; Armando J Espadas-Alvarez; Linda Garcés-Ramírez; Oriana Hidalgo-Alegria; Fidel De La Cruz-López; Daniel Martinez-Fong Journal: J Immunol Res Date: 2020-11-16 Impact factor: 4.818