ERK1/2 MAPK signaling in hypothalamic paraventricular nucleus contributes to sympathetic excitation in rats with heart failure after myocardial infarction

American Journal of Physiology. Heart and Circulatory Physiology
Yang YuRobert B Felder

Abstract

Brain MAPK signaling pathways are activated in heart failure (HF) induced by myocardial infarction and contribute to augmented sympathetic nerve activity. We tested whether decreasing ERK1/2 (also known as p44/42 MAPK) signaling in the hypothalamic paraventricular nucleus (PVN), a forebrain source of presympathetic neurons, would reduce the upregulation of sympathoexcitatory mediators in the PVN and augmented sympathetic nerve activity in rats with HF. Sprague-Dawley rats underwent left anterior descending coronary artery ligation to induce HF, with left ventricular dysfunction confirmed by echocardiography. One week after coronary artery ligation or sham operation, small interfering (si)RNAs targeting ERK1/2 or a nontargeting control siRNA was microinjected bilaterally into the PVN. Experiments were conducted 5-7 days later. Confocal images revealed reduced phosphorylated ERK1/2 immunofluorescence in the PVN of HF rats treated with ERK1/2 siRNAs compared with HF rats treated with control siRNA. Western blot analysis confirmed significant reductions in both total and phosphorylated ERK1/2 in the PVN of HF rats treated with ERK1/2 siRNAs along with reduced expression of renin-angiotensin system components and inflammatory mediat...Continue Reading

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Citations

Aug 17, 2016·Autonomic Neuroscience : Basic & Clinical·Hong Zheng, Kaushik P Patel
Feb 1, 2018·Naunyn-Schmiedeberg's Archives of Pharmacology·Juan Antonio García-CarmonaMaria Luisa Laorden
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Aug 9, 2016·American Journal of Physiology. Heart and Circulatory Physiology·Shun-Guang WeiRobert B Felder
Oct 6, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Yang YuRobert B Felder
Feb 9, 2019·American Journal of Physiology. Heart and Circulatory Physiology·Lingfang ZhuangKang Chen
Mar 30, 2019·American Journal of Physiology. Heart and Circulatory Physiology·Lucas A C SouzaYumei Feng
Aug 6, 2017·American Journal of Physiology. Heart and Circulatory Physiology·Song T YaoClive N May
Nov 16, 2016·Evidence-based Complementary and Alternative Medicine : ECAM·Min ZhengShu Zhang
Jan 17, 2020·International Journal of Molecular Sciences·So-Hyeon Hong, Kyung Mook Choi
Dec 19, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Shun-Guang WeiRobert B Felder
Sep 3, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Hui WangYufei Li

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