Author + information
- 1The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China
- 2Emergency Department, Qilu Hospital of Shandong University, Jinan, Shandong, China
Much effort has been dedicated to exploring the mechanisms of IPC, and the GJ is one of the proposed targets of IPC. Several lines of evidence have indicated that NO affects GJ permeability regulation and expression of connexin isoforms. S-nitrosylation of connexin43 by NO exerts a major influence in IPC-induced cardioprotection. The aim of article is to discuss the signaling pathways of NO in regulating GJ during IPC.
After induction of anesthesia with pentobarbital sodium (40 mg/kg; intraperitoneal injection), rats were ventilated artificially with a volume-controlled rodent respirator at 70 strokes/min. The hearts were rapidly excised and mounted on a Langendorff apparatus and retrogradely perfused with modified Krebs-Henseleit (K-H) solution. The solution was saturated with 95% O2 and 5% CO2 at constant pressure (75mmHg) and temperature (37°C). Eighty-four male Wistar rats (200-250 g) were randomly assigned to six groups receiving the following treatments, including sham-operated (SO) group, myocardial ischemia (MI) group, ischemic preconditioning (IPC+MI) group, SNAP pretreatment (SNAP+MI) group, ODQ pretreatment (IPC+ODQ) group, ascorbate pretreatment (IPC+ ascorbate) group and ODQ+ ascorbate pretreatment (IPC+ ascorbate+ ODQ). Western blotting and histological stain were used to detect protein changes and gap junction coupling.
1. Ischemia resulted in decreased SNO-proteins level, which was abrogated by IPC;
2. Ischemia induces decrease of GSNOR protein, and IPC increased level of GSNOR;
3. NO induced closure of chemical GJ with preservation of SNO-Cx43 in vivo;
4. The blockage of NO-mediated sGC/cGMP/PKG signaling pathway increased SNO-Cx43 level.
IPC-induced NO generation induced activation of SNO-Cx43, which involved the chemical GJ uncoupling.