Hoque A M, Marczin N, Catravas J D, Fuchs L C
Department of Pharmacology & Toxicology, Medical College of Georgia, Augusta 30912, USA.
Shock. 1996 Nov;6(5):365-70. doi: 10.1097/00024382-199611000-00011.
Lipopolysaccharide (LPS)-induced hypotension and impaired aortic contraction to norepinephrine (NE) are thought to be consequent to induction of nitric oxide synthase (iNOS). Anesthesia is often employed in studies of the mechanisms mediating LPS-induced cardiovascular dysfunction in rats. Since sympathetic nervous system activity and compensatory mechanisms can be altered by anesthesia, this study was designed to determine a) if the cardiovascular dysfunction associated with LPS (5 mg/kg, i.v.)-induced endotoxin shock is enhanced in anesthetized compared with conscious male Wistar rats, and b) the potential role of iNOS in these responses to LPS. Arterial pressure and heart rate were continuously measured via a femoral arterial cannula. Six hours after LPS, conscious rats had a stable mean arterial pressure (MAP) and were tachycardic, while anesthetized rats showed a significant decrease in MAP without tachycardia. Small mesenteric arterioles (200-300 microns) were isolated, and the endothelium was removed six h after LPS. Intraluminal diameter was continuously recorded while vessels were maintained at a constant intraluminal pressure of 40 mmHg. Norepinephrine-induced contraction and oscillations/min were impaired to a greater extent in arterioles from LPS-treated anesthetized rats than in those from conscious rats. Calcium-dependent and -independent nitric oxide formation, reflected as cGMP accumulation, were also determined in aortic rings treated with a chelator of Ca2+, EGTA, or the inhibitor of nitric oxide synthase activity, L-NAME. In rings from saline-treated conscious and anesthetized rats, cGMP accumulation was significantly reduced by EGTA and L-NAME, indicating calcium-dependent constitutive (cNOS) activity. However, in aortic rings from LPS-treated conscious and anesthetized rats, cGMP accumulation was not affected by EGTA and was significantly greater in rings from anesthetized vs. conscious rats. These results suggest that cardiovascular dysfunction is more prominent in LPS-treated anesthetized vs. conscious rats. This effect may be related to increased induction of iNOS in the presence of anesthesia.
脂多糖（LPS）诱导的低血压以及主动脉对去甲肾上腺素（NE）收缩反应受损被认为是一氧化氮合酶（iNOS）诱导的结果。在研究介导大鼠LPS诱导的心血管功能障碍机制的实验中常采用麻醉。由于麻醉会改变交感神经系统活性和代偿机制，本研究旨在确定：a）与清醒雄性Wistar大鼠相比，麻醉状态下LPS（5mg/kg，静脉注射）诱导的内毒素休克相关的心血管功能障碍是否会加重；b）iNOS在这些对LPS反应中的潜在作用。通过股动脉插管连续测量动脉血压和心率。LPS注射6小时后，清醒大鼠平均动脉压（MAP）稳定且心率加快，而麻醉大鼠MAP显著降低且无心率加快。分离小肠系膜动脉（200 - 300微米），LPS注射6小时后去除血管内皮。在血管腔内压力维持在40mmHg恒定值时连续记录管腔直径。LPS处理的麻醉大鼠的小动脉中，去甲肾上腺素诱导的收缩和每分钟振荡次数比清醒大鼠的小动脉受损程度更大。在用钙离子螯合剂乙二醇双四乙酸（EGTA）或一氧化氮合酶活性抑制剂L - 硝基精氨酸甲酯（L - NAME）处理的主动脉环中，还测定了反映为环磷酸鸟苷（cGMP）积累的钙依赖性和非钙依赖性一氧化氮生成。在生理盐水处理的清醒和麻醉大鼠的主动脉环中，EGTA和L - NAME显著降低了cGMP积累，表明存在钙依赖性组成型（cNOS）活性。然而，在LPS处理的清醒和麻醉大鼠的主动脉环中，EGTA对cGMP积累无影响，且麻醉大鼠主动脉环中的cGMP积累显著高于清醒大鼠。这些结果表明，与清醒大鼠相比，LPS处理的麻醉大鼠心血管功能障碍更显著。这种效应可能与麻醉状态下iNOS诱导增加有关。
