Regulatory effects of myoendothelial gap junction on vascular reactivity after hemorrhagic shock in rats.
Myoendothelial gap junction (MEGJ), one kind of gap junction between vascular endothelial cell and vascular smooth muscle cell, can transmit electrical and chemical signals to keep the electric and machinery activity synchronism of vasculature. After severe trauma or shock, vascular reactivity to vasoconstrictors or vasodilators is greatly reduced. However, whether MEGJ participates in the regulation of vascular reactivity after hemorrhagic shock, what type of MEGJ is involved, and what is the possible mechanism are unknown. With the hemorrhagic shock Sprague-Dawley rats and their superior mesenteric arteries (SMAs), the effects of 18alpha-glycyrrhetic acid, a lipophilic aglycone that disrupts gap junction plaques, on vascular contractile response to norepinephrine (endothelium-independent vascular constrictor), myricetin (endothelium-dependent vasoconstrictor) and relaxation reactivity to sodium nitroprusside (endothelium-independent vasodilator), and acetylcholine (Ach; endothelium-dependent vasodilator) were observed. Meanwhile, the relationship of the mRNA/protein expression of connexins 37, 40, and 43(Cx40 and Cx43) to the changes of vascular reactivity after hemorrhagic shock and the effect of antisense oligodeoxynucleotide of Cx40 or Cx43 on vascular calcium sensitivity and vascular reactivity were investigated. The results indicated that 18alpha-glycyrrhetic acid antagonized myricetin and Ach-induced SMA reactivity, but had no effect on norepinephrine- and sodium nitroprusside-induced vascular response. The mRNA and protein expression of Cx37 and Cx40 of SMA were negatively associated with the vascular reactivity, whereas Cx43 seemed to be a positive relationship to vascular reactivity. Antisense oligodeoxynucleotide of Cx40 significantly increased the calcium sensitivity, myricetin-induced vasoconstriction, and Ach-induced vasodilation, whereas antisense oligodeoxynucleotide of Cx43 depressed them. It was suggested that MEGJ plays an important role in the regulation of endothelium-dependent vascular reactivity after hemorrhagic shock. The involved types were mainly Cx40 and Cx43. The possible mechanism that Cx40/Cx43 regulates the endothelium-dependent vasoconstrictor reactivity may be related to their regulating effects on the calcium sensitivity of vascular smooth muscle cell.
Ming
Jia
J
State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, The Third Military University, Chongqing, People's Republic of China.
Li
Tao
T
Zhang
Yuan
Y
Xu
Jing
J
Yang
Guangming
G
Liu
Liangming
L
D000818:Animals; D017630:Connexins / Q000096:biosynthesis; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D017629:Gap Junctions / Q000378:metabolism* / Q000473:pathology; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D008638:Mesenteric Arteries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents / Q000494:pharmacology
D017630:Connexins; D020319:Oligodeoxyribonucleotides, Antisense; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C119129:18alpha-glycyrrhetinic acid; D006034:Glycyrrhetinic Acid