ATP-MgCl2 restores depressed endothelial cell function after hemorrhagic shock and resuscitation.
Although ATP-MgCl2 produces beneficial effects following various adverse circulatory conditions, it remains unknown whether this agent restores the depressed endothelial cell function [i.e., the reduced release of endothelium-derived nitric oxide (EDNO) and endothelium-derived contracting factors (EDCF)] in a model of trauma-hemorrhage and resuscitation. To determine this, rats underwent laparotomy (i.e., trauma induced), were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of shed blood volume was returned in the form of Ringer lactate (RL). The animals were then resuscitated with four times the volume of maximal bleedout with RL, following which ATP-MgCl2 (50 mumol/kg body wt) or saline was administered. At 1.5 h postresuscitation, the aorta and superior mesenteric artery (SMA) were isolated, and dose-responses for acetylcholine (ACh, an endothelium-dependent vasodilator, via EDNO) and nitroglycerin (an endothelium-independent vasodilator) were determined. In addition, hypoxia-induced contraction, a process mediated by EDCF, was assessed. The results indicate that the decreased endothelium-dependent relaxation after hemorrhage (sham 94 +/- 3 and 97 +/- 3% vs. hemorrhage 64 +/- 5 and 57 +/- 11% at 10-5 M ACh in aorta and SMA, respectively, P < 0.05) was restored with ATP-MgCl2 treatment. In contrast, there was no significant difference in nitroglycerin-induced relaxation. Moreover, the decreased hypoxia-induced aortic contraction after hemorrhage (sham 221 +/- 26 mg/ring vs. hemorrhage 124 +/- 22 mg/ring, P < 0.05) was attenuated by administration of ATP-MgCl2.(ABSTRACT TRUNCATED AT 250 WORDS)
Wang
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Department of Surgery, Michigan State University, East Lansing 48824, USA.
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Chaudry
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D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000255:Adenosine Triphosphate; D005996:Nitroglycerin; D000109:Acetylcholine; D009638:Norepinephrine