Ryanodine receptor 2 contributes to hemorrhagic shock-induced bi-phasic vascular reactivity in rats

• Published in: Acta pharmacologica Sinica 2014-11, Vol.35 (11), p.1375-1384
• Main Authors: Zhou, Rong, Ding, Xiao-li, Liu, Liang-ming
• Format: Article
• Language: English
• Subjects: Animals; Arterial Pressure; Biomedical and Life Sciences; Biomedicine; Caffeine - pharmacology; Calcium Channel Agonists - pharmacology; Calcium Signaling; Cell Hypoxia; Cells, Cultured; Disease Models, Animal; Dose-Response Relationship, Drug; Immunology; Internal Medicine; Medical Microbiology; Mesenteric Artery, Superior - metabolism; Mesenteric Artery, Superior - physiopathology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - physiopathology; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Norepinephrine - pharmacology; Original; original-article; Pharmacology/Toxicology; Rats, Sprague-Dawley; RNA Interference; Ryanodine Receptor Calcium Release Channel - drug effects; Ryanodine Receptor Calcium Release Channel - genetics; Ryanodine Receptor Calcium Release Channel - metabolism; Sarcoplasmic Reticulum - metabolism; SD大鼠; Shock, Hemorrhagic - genetics; Shock, Hemorrhagic - metabolism; Shock, Hemorrhagic - physiopathology; siRNA; Time Factors; Transfection; Vaccine; Vasoconstriction - drug effects; Vasoconstrictor Agents - pharmacology; VSMC; 双相; 受体; 失血性休克; 血管反应性; 血管平滑肌细胞
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2014.83

Aim： Ryanodine receptor 2 （RyR2） is a critical component of intracellular Ca2＋ signaling in vascular smooth muscle cells （VSMCs）. The aim of this study was to investigate the role of RyR2 in abnormal vascular reactivity after hemorrhagic shock in rats. Methods： SD rats were hemorrhaged and maintained mean arterial pressure （MAP） at 40 mmHg for 30 min or 2 h, and then superior mesenteric arteries （SMA） rings were prepared to measure the vascular reactivity. In other experiments, SMA rings of normal rats and rat VSMCs were exposed to a hypoxic medium for 10 min or 3 h. SMA rings of normal rats and VSMCs were transfected with siRNA against RyR2. Intracellular Ca2~ release in VSMCs was assessed using Fura-2/AM. Results： The vascular reactivity of the SMA rings from hemorrhagic rats was significantly increased in the early stage （30 min）, but decreased in the late stage （2 h） of hemorrhagic shock. Similar results were observed in the SMA rings exposed to hypoxia for 10 rain or 3 h. The enhanced vascular reactivity of the SMA rings exposed to hypoxia for 10 min was partly attenuated by transfection with RyR2 siRNA, whereas the blunted vascular reactivity of the SMA rings exposed to hypoxia for 3 h was partly restored by transfection with RyR2 siRNA. Treatment with the RyR agonist caffeine （1 mmol/L） significantly increased Ca2＋ release in VSMCs exposed to hypoxia for 10 min or 3 h, which was partially antagonized by transfection with RyR2 siRNA. Conclusion： RyR2-mediated Ca2＋ release contributes to the development of bi-phasic vascular reactivity induced by hemorrhagic shock or hypoxia.