Parker J L, Keller R S, DeFily D V, Laughlin M H, Novotny M J, Adams H R
John M. Dalton Research Center, University of Missouri, Columbia 65211.
Am J Physiol. 1991 Mar;260(3 Pt 2):H832-41. doi: 10.1152/ajpheart.1991.260.3.H832.
The purpose of this study was to determine whether intrinsic contraction-relaxation properties of coronary arteries are altered during acute gram-negative endotoxemia. Coronary vascular smooth muscle (VSM) was evaluated in vitro using large and small left circumflex coronary ring preparations isolated from dogs 4 h after administration of either saline (control; C) or 1.5 mg/kg Escherichia coli endotoxin (ET). ET dogs exhibited marked systemic hypotension and cardiovascular depression throughout the 4-h in vivo phase of the study accompanied by reduction in total left ventricular myocardial blood flow. Isolated coronary vessels were stretched to the apex of the length-contractile tension curve; no differences were observed in length-active or length-passive tension (vessel compliance) relationships between C and ET vessels. Isometric contractions produced by K+ and prostaglandin F2 alpha (PGF2 alpha) were similar in C and ET coronary arteries. VSM relaxant responses to nitroprusside (NP; 10(-10) to 10(-4) M) were also similar in C and ET vessels. In contrast to the apparent lack of effect of ET on directly acting VSM agents, relaxation responses to the endothelial-dependent vasodilator acetylcholine (ACh) were significantly less in ET vessels. Impaired vasodilator response to ACh was not improved by in vivo treatment with the combination antioxidant therapy of allopurinol, superoxide dismutase, and catalase. We conclude that both depolarization (K+) and receptor (PGF2 alpha)-mediated contractile mechanisms, as well as basal cGMP (NP)-mediated vasodilator mechanisms, remained functional in coronary vasculature during acute endotoxemia. Inhibition of ACh-mediated relaxation in ET vessels suggests altered endothelial-dependent vasodilation in coronary arteries during endotoxemia, but this change did not seem to be associated causally with oxygen free radicals.
本研究的目的是确定在急性革兰氏阴性内毒素血症期间冠状动脉的内在收缩 - 舒张特性是否发生改变。使用从给予生理盐水（对照组；C）或1.5mg/kg大肠杆菌内毒素（ET）4小时后的犬分离出的左旋冠状动脉大环和小环制剂，在体外评估冠状血管平滑肌（VSM）。在研究的4小时体内阶段，ET组犬表现出明显的全身性低血压和心血管抑制，同时左心室心肌总血流量减少。将分离的冠状血管拉伸至长度 - 收缩张力曲线的顶点；C组和ET组血管在长度 - 主动或长度 - 被动张力（血管顺应性）关系方面未观察到差异。K⁺和前列腺素F2α（PGF2α）产生的等长收缩在C组和ET组冠状动脉中相似。C组和ET组血管对硝普钠（NP；10⁻¹⁰至10⁻⁴M）的VSM舒张反应也相似。与ET对直接作用的VSM药物明显缺乏作用相反，ET组血管对内皮依赖性血管舒张剂乙酰胆碱（ACh）的舒张反应明显较小。用别嘌呤醇、超氧化物歧化酶和过氧化氢酶的联合抗氧化疗法进行体内治疗并不能改善对ACh的血管舒张反应受损情况。我们得出结论，在急性内毒素血症期间，去极化（K⁺）和受体（PGF2α）介导的收缩机制以及基础cGMP（NP）介导的血管舒张机制在冠状血管系统中仍保持功能。ET组血管中ACh介导的舒张受到抑制表明内毒素血症期间冠状动脉中内皮依赖性血管舒张发生改变，但这种变化似乎与氧自由基没有因果关系。
