Peroxynitrite leads to arteriolar smooth muscle cell membrane hyperpolarization and low vasoreactivity in severe shock.
This paper aimed to study the mechanism of vascular hyporeactivity during severe hemorrhagic shock. Rats were divided into control and shock group. Membrane potential of arteriolar strips was measured with intracellular recording method and membrane potential changes in arteriolar smooth muscle cells (ASMC) were recorded with membrane potential sensitive fluorescent dye (DiBAC4) and confocal microscopy. Hyperpolarization of ASMC membrane appeared at the late stage of shock, which correlated to low vasoreactivity. Glybenclamide, an inhibitor of K(ATP) channel reversed the hyperpolarizing effect. S-nitroso-N-acetylpenicillamine (SNAP), a donor of NO, in a higher concentration (400 mol/l) caused membrane hyperpolarization in control and shock group, which was completely reversed by application of Tiron, a scavenger of O2-. The hyperpolarizing effect of SNAP was decreased by ODQ, glybenclamide and (or) charybdotoxin. It is concluded that hyperpolarization of ASMC leads to vascular hyporeactivity. Peroxynitrite (OONO-) involves in the development of hyperpolarization in severe shock. The production of cGMP and activation of K(ATP) and K(Ca) channel contribute to the hyperpolarizing effect of OONO-*.
Zhao
K S
KS
Department of Pathophysiology, First Military Medical University, Guangzhou, China. zhaoks@fimmu.edu.cn
Liu
J
J
Yang
G Y
GY
Jin
C
C
Huang
Q
Q
Huang
X
X
D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001160:Arterioles; D018999:Charybdotoxin / Q000494:pharmacology; D006152:Cyclic GMP / Q000502:physiology; D004347:Drug Interactions; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000166:cytology; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009566:Nitrates / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D014665:Vasodilator Agents / Q000494:pharmacology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D016166:Free Radical Scavengers; D006146:Guanidines; D009566:Nitrates; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D015221:Potassium Channels; D011810:Quinoxalines; C110881:S-nitro-N-acetylpenicillamine; D014665:Vasodilator Agents; D018999:Charybdotoxin; C039642:peroxynitric acid; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D001120:Arginine; D010396:Penicillamine; D006152:Cyclic GMP; D011188:Potassium; C004479:pimagedine; D005905:Glyburide; D009638:Norepinephrine