Abstract
To investigate the role of protein kinase G (PKG) in blocking post-shock mesenteric lymph (PSML) return ameliorating the calcium sensitivity in hemorrhagic shock rats. Male Wistar rats were randomly divided into sham, shock, shock+ligation (shock plus mesenteric lymph duct ligation (MLDL)), shock+drainage (shock plus PSML drainage) groups. After shock (hypotension 40 mm Hg) for three hours or corresponding times, the superior mesenteric artery (SMA) was taken out for detecting the PKG and phospho PKG (p-PKG) contents, and the vascular rings of SMA were prepared for assaying the calcium sensitivity using an isolated organ perfusion system. The PKG and p-PKG contents of SMA in shock group were significantly increased than that of sham group, and MLDL or PSML drainage reducing the levels of PKG and p-PKG. Meanwhile, the vascular calcium sensitivity in shock group was significantly lower than that of sham group, MLDL or PSML drainage enhanced the calcium sensitivity. After incubating with PKG regulators in shock+ligation and shock+drainage groups, the PKG agonist 8Br-cGMP reduced the contractility of vascular rings to gradient calcium ions and Emax and the PKG inhibitor agonist KT5823 elevated the calcium sensitivity significantly. Protein kinase G plays an important role in post-shock mesenteric lymph blockage improving vascular calcium sensitivity.
Highlights
One of the hallmarks of severe shock is refractory hypotension, during which the arteries lose responsiveness to vasoactive agents, such as norepinephrine (NE), epinephrine, and dopamine[1]
Our previous study showed that the mesenteric lymph duct ligation (MLDL) and mesenteric lymph drainage (MLD), which blocking the post-shock mesenteric lymph (PSML) return, both improved the reactivity and calcium sensitivity of vascular rings isolated from severe hemorrhagic shock rats[5]
On the basis of an animal experiment that the PSML return involved in the vascular hyporeactivity and calcium desensitization induced by hemorrhagic shock[5], the present paper documented that the mesenteric lymph duct ligation or mesenteric lymph drainage decreased the elevated expression of Protein kinase G (PKG) protein and activity of p-PKG induced by hemorrhagic shock in the tissue of superior mesenteric artery (SMA)
Summary
One of the hallmarks of severe shock is refractory hypotension, during which the arteries lose responsiveness to vasoactive agents, such as norepinephrine (NE), epinephrine, and dopamine[1]. The vascular hyporeactivity is an important factor in irreversible shock[2], calcium desensitization is one of the mechanisms of vascular hyporeactivity[3,4]. Our previous study showed that the mesenteric lymph duct ligation (MLDL) and mesenteric lymph drainage (MLD), which blocking the post-shock mesenteric lymph (PSML) return, both improved the reactivity and calcium sensitivity of vascular rings isolated from severe hemorrhagic shock rats[5]. The mechanism by which PSML blunts the vascular reactivity and calcium sensitivity remain unclear. The previous studies showed that PKG was involved in the calcium desensitization of vascular smooth muscle after hemorrhagic shock, which was possibly related to MLCK3,7. PKG plays an important role on the regulation of calcium sensitivity. Whether PKG involved in PSML blockage improving calcium sensitivity is still unknown
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