Propofol Attenuates Acetylcholine-induced Pulmonary Vasorelaxation: Role of Nitric Oxide and Endothelium-derived Hyperpolarizing Factors

Background: The mechanism by which propofol selectively attenuates the pulmonary vasodilator response to acetylcholine is unknown. The goals of this study were to identify the contributions of endogenous endothelial mediators (nitric oxide [NO], prostacyclin, and endothelium-derived hyperpolarizing factors [EDHFs]) to acetylcholine-induced pulmonary vasorelaxation, and to delineate the extent to which propofol attenuates responses to these endothelium-derived relaxing factors.

Methods: Canine pulmonary arterial rings were suspended for isometric tension recording. The effects of propofol on the vasorelaxation responses to acetylcholine, bradykinin, and the guanylyl cyclase activator, SIN-1, were assessed in phenylephrine-precontracted rings. The contributions of NO, prostacyclin, and EDHFs to acetylcholine-induced vasorelaxation were assessed in control and propofol-treated rings by pretreating the rings with a NO synthase inhibitor (l-NAME), a cyclooxygenase inhibitor (indomethacin), and a cytochrome P450 inhibitor (clotrimazole or SKF 525A) alone and in combination.

Results: Propofol caused a dose-dependent rightward shift in the acetylcholine dose-response relation, whereas it had no effect on the pulmonary vasorelaxant responses to bradykinin or SIN-1. Cyclooxygenase inhibition only attenuated acetylcholine-induced relaxation at high concentrations of the agonist. NO synthase inhibition and cytochrome P450 inhibition each attenuated the response to acetylcholine, and combined inhibition abolished the response. Propofol further attenuated acetylcholine-induced relaxation after NO synthase inhibition and after cytochrome P450 inhibition.     

Inhaled Nitric Oxide Pretreatment But Not Post-treatment Attenuates Ischemia-Reperfusion-induced Pulmonary Microvascular Leak

Background: Ischemia-reperfusion (I/R) pulmonary edema probably reflects a leukocyte-dependent, oxidant-mediated mechanism. Nitric oxide (NO) attenuates leukocyte-endothelial cell interactions and I/R-induced microvascular leak. Cyclic adenosine monophosphate (cAMP) agonists reverse and prevent I/R-induced microvascular leak, but reversal by inhaled NO (INO) has not been tested. In addition, the role of soluble guanylyl cyclase (sGC) activation in the NO protection effect is unknown.

Methods: Rat lungs perfused with salt solution were grouped as either I/R, I/R with INO (10 or 50 ppm) on reperfusion, or time control. Capillary filtration coefficients (Kfc) were estimated 25 min before ischemia (baseline) and after 30 and 75 min of reperfusion. Perfusate cell counts and lung homogenate myeloperoxidase activity were determined in selected groups. Additional groups were treated with either INO (50 ppm) or isoproterenol (ISO-10 micro Meter) after 30 min of reperfusion. Guanylyl cyclase was inhibited with 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ-15 micro Meter), and Kfc was estimated at baseline and after 30 min of reperfusion.

Results: (1) Inhaled NO attenuated I/R-induced increases in Kfc. (2) Cell counts were similar at baseline. After 75 min of reperfusion, lung neutrophil retention (myeloperoxidase activity) and decreased perfusate neutrophil counts were similar in all groups. (3) In contrast to ISO, INO did not reverse microvascular leak. (4) 8-bromoguanosine 3',5'-cyclic monophosphate (8-br-cGMP) prevented I/R-induced microvascular leak in ODQ-treated lungs, but INO was no longer effective.     

Cerebellar Nitric Oxide Is Increased during Isoflurane Anesthesia Compared to Halothane Anesthesia: A Microdialysis Study in Rats

Background: This study examined the influences of isoflurane versus halothane anesthesia on basal and agonist-stimulated nitric oxide in the cerebellum of intact rats. Nitric oxide was measured using the hemoglobin-trapping method in an in vivo microdialysis technique. This method uses the stoichiometric reaction of nitric oxide with oxyhemoglobin to produce methemoglobin and nitrate; the change in methemoglobin concentration is measured spectrophotometrically to estimate nitric oxide concentration.

Methods: Male Wistar rats were anesthetized with isoflurane (1.4%) or halothane (1.2%), mechanically ventilated and paralyzed (intravenous pancuronium, 1 mg/kg). Microdialysis probes were implanted into the cerebellum. Bovine oxyhemoglobin dissolved in artificial cerebrospinal fluid was pumped through the probe (2 [micro sign]l/ min) and assayed at 15-min intervals. The glutamatergic agonist, kainic acid (KA, 5 mg/kg, intraarterially), was used to stimulate nitric oxide production. NG-nitro L-arginine methyl ester (L-NAME, 40 mg/kg, intravenously) was used to inhibit nitric oxide synthase.

Results: Unstimulated cerebellar nitric oxide concentrations were stable and greater during anesthesia with isoflurane (532 +/- 31 nM; mean +/- SEM) than with halothane (303 +/- 23 nM). L-NAME pretreatment reduced nitric oxide concentrations during isoflurane, but not halothane, anesthesia. Infusion of KA increased nitric oxide in both groups; however, the increase in nitric oxide was significantly greater during isoflurane anesthesia. Pretreatment with L-NAME inhibited the response to KA in both groups.     

Interaction of Isoflurane and Nitrous Oxide Combinations Similar for Median Electroencephalographic Frequency and Clinical Anesthesia

Background: The volatile anesthetic sparing effect of nitrous oxide in clinical studies is less than might be expected from the additivity of minimum alveolar concentration values. Other studies identify nonadditive interactions between isoflurane and nitrous oxide. The aim of this study was to quantify the interaction of isoflurane and nitrous oxide at a constant median electroencephalographic frequency.

Methods: Twenty-five patients were studied during laparotomies. Nitrous oxide was randomly administered in concentrations of 0, 20, 40, 60, and 75 vol%, to ten patients for each nitrous oxide concentration. Isoflurane vaporizer settings were chosen so that the median electroencephalographic frequency was held between 2 and 3 Hz. The relationship between nitrous oxide concentrations and required isoflurane concentrations was examined with the method of isoboles.

Results: Nitrous oxide linearly decreased the isoflurane requirement. Addition of every 10 vol% of nitrous oxide decreases the isoflurane requirement by approximately 0.04 vol%. The total anesthetic requirement of isoflurane and nitrous oxide, expressed in terms of previously reported minimum alveolar concentration values, increased significantly with increasing nitrous oxide concentrations.     

Usefulness of Nitric Oxide Treatment for Pulmonary Hypertensive Infants during Cardiac Anesthesia

Background: The beneficial effect of inhaled nitric oxide (NO) on pulmonary hypertension is well known. However, the indications for NO inhalation therapy for pulmonary hypertension associated with congenital heart lesions are still unclear. The aim of the current study was to seek a measure that would predict the effectiveness of inhaled NO in infants undergoing cardiac surgery.

Methods: Forty-six infants with pulmonary hypertension were studied. Pulmonary vascular resistance (PVR) measured at the time of cardiac catheterization was used as an indicator and compared with pulmonary arterial pressure/systemic blood pressure ratio (Pp/Ps) at the time of weaning from cardiopulmonary bypass. The effect of 40 ppm of inhaled NO for 15 min was evaluated in patients whose Pp exceeded systemic values.

Results: Preoperative PVR correlated positively with Pp/Ps at the time of weaning from cardiopulmonary bypass (r2 = 0.86;P < 0.05; n = 46). A Pp/Ps greater than or equal to 1 was not observed in any cases in which the preoperative PVR values were less than 7 Wood units m2; Pp/Ps ratio greater than or equal to 1 occurred in four patients. Each of these had PVR values greater than 7 Wood units m2. Three of these patients who had PVR values in the 7-12 Wood units m2 range were responsive to inhaled NO. The fourth patient, whose PVR value was greater than 15 Wood units m2, was unresponsive. Lung biopsy specimens were obtained in two patients whose preoperative PVR values were greater than 10 Wood units m2.     

Spinal Cord Motoneuron Excitability during Isoflurane and Nitrous Oxide Anesthesia

Background: Recent evidence suggests that the spinal cord is an important site of anesthesia that is necessary for surgical immobility, but the specific effect of anesthetics within the spinal cord is unclear. This study assessed the effect of isoflurane and nitrous oxide on spinal motoneuron excitability by monitoring the H-reflex and the F wave.

Methods: Eight adult patients, categorized as American Society of Anesthesiologists physical status 1 or 2, who were undergoing elective orthopedic surgery were anesthetized with 0.6, 0.8, 1.0, and 1.2 times the estimated minimum alveolar concentration (MAC) of isoflurane. Nitrous oxide was added in graded concentrations of 30%, 50%, and 70%, whereas the isoflurane concentration was decreased to maintain a total MAC of 1. The H-reflex of the soleus muscle and the F wave of the abductor hallucis muscle were measured before anesthesia and 15 min after each change of anesthetic concentration. Four or more trials of the H-reflex and 18 trials of the F wave were recorded at each concentration of anesthesia. The effect of the anesthetics on the H-reflex and F wave was analyzed using Dunnett's test.

Results: H-reflex amplitude was decreased to 48.4 +/- 18.6% of preanesthesia level at 0.6 MAC isoflurane and to 33.8 +/- 19.1% when isoflurane concentration increased from 0.6 MAC to 1.2 MAC. F wave amplitude and persistence decreased to 52.2 +/- 33.6% and 44.4 +/- 26% of baseline at 0.6 MAC isoflurane, and to 33.8 +/- 26% and 21.7 +/- 22.8% at 1.2 MAC isoflurane. Isoflurane plus nitrous oxide (total 1 MAC) decreased H-reflex amplitude to 30.4-33.3% and decreased F wave persistence to 42.8-56.3% of baseline.     

Halothane but Not Isoflurane Attenuates Interleukin 1β- induced Nitric Oxide Synthase in Vascular Smooth Muscle

Background: Inducible nitric oxide synthase (iNOS) is induced by endotoxin or cytokines, such as interleukin (IL)-1, through a protein synthesis pathway. Halothane reportedly inhibits protein synthesis in various tissues. The aim of the current study was to examine the effect of halothane on the IL-1[beta]-evoked induction of NOS in vascular smooth muscle.

Methods: After removal of the endothelium, arterial rings of rat aorta were mounted in an isometric force recording system. The effects of halothane (1.0-3.0%) or isoflurane (3.0%) on IL-1[beta] (20 ng/ml)-induced inhibition of the contractile responses to KCl (30 mm) and phenylephrine (10-9~10-5 m) were studied. The cyclic guanosine monophosphate and cyclic adenosine monophosphate contents were determined by radioimmunoassay. Expression of iNOS and iNOS mRNA were measured by Western or Northern blot analysis, respectively.

Results: Halothane (1.0-3.0%) but not isoflurane (3%) significantly reduced the IL-1[beta]-induced inhibition of contraction in a concentration-dependent manner. The cyclic guanosine monophosphate content of the vascular smooth muscle increased significantly after a 5-h exposure to IL-1[beta]. Halothane at 3.0% significantly inhibited the increase in cyclic guanosine monophosphate content induced by IL-1[beta]. Halothane had no effect on cyclic adenosine monophosphate content. IL-1[beta]-induced expression of iNOS and iNOS mRNA in the rat aorta were inhibited significantly by halothane.     

Inhaled Nitric Oxide Reveals and Attenuates Endothelial Dysfunction After Lung Transplantation

Background. Maintaining endothelial function within transplanted organs may be critical to successful preservation. In this study we have evaluated the relationship between the effect of inhalation of nitric oxide and the degree of endothelial dysfunction after lung transplantation.

Methods. A left lung, which had been preserved for 24 hours, was transplanted and a right pneumonectomy was performed in 5 pigs. After a 24-hour observation period the pigs inhaled 5, 20, and 80 ppm nitric oxide, and pulmonary vascular resistance was recorded continuously. From the same donors preserved pulmonary arteries from the contralateral lung were studied simultaneously in organ baths. Acetylcholine chloride was used to elicit endothelium-dependent relaxation in vessel segments contracted with the thromboxane A₂ analogue U-46619.

Results. Maximal endothelium-dependent relaxation decreased in the preserved lungs and correlated to the pulmonary vascular resistance in the simultaneously transplanted lungs. Inhalation of nitric oxide in the pigs that had received transplants caused the pulmonary vessels to dilate in proportion to the endothelial dysfunction.

Conclusions. Preservation of lung for transplantation induces an endothelial dysfunction, and the degree of the decrease in pulmonary vascular resistance caused by nitric oxide inhalation may be an indication of the degree of this endothelial damage. The vasodilation caused by inhaled nitric oxide increases as the endothelial function deteriorates.     

Contribution of Interaction between Nitric Oxide and Cyclooxygenases to the Production of Prostaglandins in Carrageenan-induced Inflammation

Background: Nitric oxide (NO) and prostaglandins (PGs) are crucial mediators contributing to generation of inflammatory responses and pain. This study was designed to investigate the effects of peripherally released NO on cyclooxygenase (COX) expression/activation and production of PGs in carrageenan-induced inflammation.

Methods: A microdialysis probe was implanted subcutaneously into the skin of hind paws of rats. The concentrations of NO metabolites, PGE2, and 6-keto-PGF1[alpha] (metabolite of PGI2) in the dialysate were measured. Carrageenan was injected into the plantar surface of the hind paw during perfusion of the dialysis catheter with modified Ringer's solution or NG-monomethyl-l-arginine acetate. In addition, the effects of the selective COX-1 inhibitor SC-560 and the selective COX-2 inhibitor NS-398 on the production of NO, PGE2, and 6-keto-PGF1[alpha] were examined. Western blotting was performed to evaluate the expression of COX-1 and COX-2 in the skin at the site of the inflammation.

Results: Carrageenan injection resulted in increases in the concentrations of NO, PGE2, and PGI2, and these increases were completely suppressed by NG-monomethyl-l-arginine acetate. SC-560 effectively inhibited the increase in PGE2 and PGI2 concentrations for the first 2 h, and NS-398 inhibited 3-6 h after carrageenan. Western blot analysis showed that the concentrations of both COX-1 and COX-2 in the skin increased after carrageenan. The up-regulation of COX-1 in the skin was observed 3 and 6 h after carrageenan and was not suppressed in the rats treated with NG-monomethyl-l-arginine acetate. The up-regulation of COX-2 in the skin was also observed 3 and 6 h after carrageenan and was completely suppressed in the rats treated with NG-monomethyl-l-arginine acetate.     

Attenuated Hypoxic Pulmonary Vasoconstriction during Isoflurane Anesthesia Is Abolished by Cyclooxygenase Inhibition in Chronically Instrumented Dogs

Background: Hypoxic pulmonary vasoconstriction (HPV) is a homeostatic mechanism whereby gas exchange is improved through the diversion of blood flow away from poorly oxygenated regions of the lung. The effect of isoflurane anesthesia on HPV is unclear. Using a chronically instrumented canine model, it was hypothesized that isoflurane anesthesia would attenuate HPV compared to the response measured in the same animal in the conscious state. Moreover, because volatile anesthetics increase the production of cyclooxygenase metabolites, it was hypothesized that attenuation of HPV during isoflurane anesthesia would be abolished by cyclooxygenase inhibition.

Methods: Left pulmonary vascular pressure-flow plots were generated in chronically instrumented dogs by measuring the pulmonary vascular pressure gradient (pulmonary arterial pressure-left atrial pressure) and left pulmonary blood flow during inflation of a hydraulic occluder implanted around the right main pulmonary artery. In protocol 1 (n = 7), left pulmonary vascular pressure-flow plots were generated during normoxia and hypoxia (systemic arterial PO2 approximately 50 mmHg) in the conscious and isoflurane-anesthetized states. In protocol 2 (n = 7), left pulmonary vascular pressure-flow plots were generated during normoxia and hypoxia (1) in the conscious state, (2) in the conscious state after inhibition of the cyclooxygenase pathway with indomethacin, and (3) during isoflurane anesthesia after cyclooxygenase inhibition.

Results: In both the conscious and isoflurane-anesthetized states, the magnitude of HPV was dependent on the level of left pulmonary blood flow. Compared to the response measured in the conscious state, the magnitude of HPV was attenuated during isoflurane anesthesia over the empirically measured range of left pulmonary blood flow. Cyclooxygenase inhibition abolished the isoflurane-induced attenuation of HPV.     

吸入一氧化氮出现肺动脉压反跳原因初探及对策

目的探讨吸入NO疗法肺动脉压出现反跳的原因和预刚防对策。方法以烟雾吸入性损伤犬模型为研究对象,对照组单纯吸氧,治疗组吸氧 NO。连续监测12小时肺动脉压和动脉血变化;正常组不致伤,用于建立组织学对照、结果肺组织NOS活性治疗组明显低于对照组（P＜0.01）;治疗组血浆ETS和AⅡ与对照组相比均有不同程度降低,ET_s（P＜0.05～0.01）,AⅡ（Ｐ＜0.05～0.01）。结论　临床长期或应用大剂量吸入NO时．应确定最低有效浓度和有计划逐渐减量,以防发生反跳。     

Role of Endothelium/Nitric Oxide and Cyclic AMP in Isoproterenol Potentiation of 17ß-Estradiol-Mediated Vasorelaxation

Background: Calcitonin gene-related peptide (CGRP) is known to have an extremely potent and prolonged vasodilator effect on the coronary arteries. Studies have shown that CGRP increased coronary blood flow and alleviated reperfusion injury in vitro. It is still unknown, however, whether exogenous CGRP has a protective effect on the reperfusion heart associated with cardiopulmonary bypass (CPB). Methods: An in vivo porcine model of CPB was established. Twenty pigs, 10 controls and 10 CGRP used animals (CGRP group), were performed a median sternotomy followed by a standard CPB. All the hearts were arrested for 45 minutes. In the CGRP group, 1mg/kg CGRP was added into the cardioplegia, and another 1mg/kg was reperfused just before the aortic cross-clamp was removed. In both groups, myocardial microvascular perfusion, coronary arterial microvessel diameter and microvessel blood flow were detected by a laser doppler flowmeter and a contact microscope with TV monitor on five consecutive time perioperatively. Result: Myocardial microvascular perfusion was significantly higher and coronary arterial microvessel diameter was larger in the CGRP group on every point of time of reperfusion compared to those in the control group. In the CGRP group, microvessel blood flow also improved significantly than that in the control group during reperfusion. Conclusion: CGRP improves myocardial microcirculation during cardiac ischemia-reperfusion associated with CPB and could become a new, potent myocardial protector.     

妇科腹腔镜手术全凭静脉麻醉与异氟醚吸入麻醉的对比研究

目的观察瑞芬太尼靶控输注复合异丙酚全凭静脉麻醉与异氟醚吸入麻醉在妇科腹腔镜手术中的应用效果。方法随意选择2008年1～12月择期妇科腹腔镜手术60例,ASA分级Ⅰ～Ⅱ级,分为2组：靶控输注瑞芬太尼复合异丙酚全凭静脉麻醉组（T组,n=30）,采用咪唑安定0.05 mg/kg,瑞芬太尼1μg/kg,异丙酚2～2.5 mg/kg及维库溴铵0.1 mg/kg快速诱导后,经口明视气管插管,维持采用瑞芬太尼靶浓度4～8 ng/ml,异丙酚4～8 mg.kg-1.h-1;异氟醚组（I组,n=30）,采用芬太尼2μg/kg,异丙酚2～2.5 mg/kg,维库溴铵0.1 mg/kg诱导,经口明视插管后,维持采用1∶1的氧气和异氟醚（维持呼气末浓度0.8～1.2 MAC）吸入麻醉。术中监测收缩压（SBP）、舒张压（DBP）、心率（HR）等指标。结果在插管后1 min（T3）,I组病人DBP、HR与基础值（T1）比较明显升高（P〈0.05）,T组病人DBP、HR则基本恢复到T1水平,2组比较差异有显著性（t=-4.277,P=0.000;t=-3.286,P=0.002）。清醒拔管时（T6）与T1比较,I组SBP、DBP、HR明显升高（P〈0.05）,而T组SBP、DBP、HR则无明显变化（P〉0.05）,2组比较差异有显著性（t=-5.461,P=0.000;t=-2.287,P=0.000;t=-4.382,P=0.000）。T组病人诱导时间、苏醒时间、拔管时间均显著短于I组（t=-6.386,P=0.000;t=-4.876,P=0.000;t=-6.632,P=0.000）。结论瑞芬太尼靶控输注复合异丙酚全凭静脉麻醉在妇科腹腔镜手术中既满足了手术要求又提高了麻醉药的可控性。     

Effects of Isoflurane Versus Fentanyl-Nitrous Oxide Anesthesia on Long-term Outcome from Severe Forebrain Ischemia in the Rat

Background: This study examined long-term outcome from severe forebrain ischemia in the rat, as a function of anesthetic given during the ischemic injury.

Methods: Rats were subjected to 10 min of near-complete forebrain ischemia while anesthetized with either 1.4% isoflurane or 70% nitrous oxide-fentanyl. Neurologic and histologic outcomes were measured at 5 days, 3 weeks, or 3 months after ischemia.

Results: At 5 days, isoflurane-anesthetized rats had less damage than did fentanyl-nitrous oxide-anesthetized rats (mean +/- SD, percent alive hippocampal CA1 neurons = 58 +/- 29 vs. 20 +/- 16, respectively; P = 0.011). This was accompanied by improved motor function in the isoflurane group (P = 0.002). At 3 weeks, there was no difference between groups for either outcome variable (percent alive CA1 neurons = 35 +/- 26 and 36 +/- 28 for isoflurane and fentanyl-nitrous oxide, respectively). Similarly, at 3 months, there was no difference between groups (percent alive CA1 neurons = 56 +/- 27 and 60 +/- 27 for isoflurane and fentanyl-nitrous oxide, respectively). Morris water maze performance at 3 months was similar between anesthetic groups and was also similar to sham performance. The percent alive CA1 neurons in the fentanyl-nitrous oxide group increased with duration of recovery (P = 0.004). There were no differences among isoflurane groups over time (5 days vs. 3 weeks, P = 0.26; 5 days vs. 3 months, P = 0.99; 3 week vs. 3 months, P = 0.32).     

Halothane and Isoflurane Inhibit Vasodilation Due to Constitutive but Not Inducible Nitric Oxide Synthase: Implications for the Site of Anesthetic Inhibition of the Nitric Oxide/Guanylyl Cyclase Signaling Pathway

Background: Inhalational anesthetics inhibit the nitric oxide-guanylyl cyclase signaling pathway, but the site of this inhibition is not yet clear. This study was designed to test the hypothesis that receptor activation or downstream signaling events leading to nitric oxide synthase activation are important sites for this inhibition by comparing the effect of anesthetics on vasodilation caused by the calcium-dependent constitutive endothelial nitric oxide synthase versus the calcium-independent inducible nitric oxide synthase.

Methods: Endothelium-intact or -denuded rat thoracic aorta rings preincubated with or without lipopolysaccharide were mounted for isometric tension measurement, constricted with phenylephrine, then relaxed with methacholine in the presence or absence of halothane (1-3%) or isoflurane (1-3%). The cyclic guanosine 3,5-monophosphate content in the endothelium-denuded rings preincubated with or without lipopolysaccharide in the presence or absence of 3% halothane or 3% isoflurane was quantified by radioimmunoassay. The activity of partially purified inducible nitric oxide synthase from activated mouse macrophage was assayed in the presence or absence of halothane (1-4%) or isoflurane (1-5%) by the conversion of sup 3 H-L-arginine to3 Hydrogen-L-citrulline.

Results: Halothane and isoflurane inhibited methacholine-stimulated, nitric oxide-mediated vasorelaxation in endothelium-intact aortic rings. Neither halothane nor isoflurane affected the vasorelaxation caused by basal endothelial nitric oxide synthase or inducible nitric oxide synthase activity. Neither anesthetic altered the cyclic guanosine 3,5-monophosphate increase caused by inducible nitric oxide synthase in the lipopolysaccharide-treated rings.     

抑制一氧化氮生物合成对门脉高压鼠血流动力学的影响

研究一氧化氮(NO)在门脉高压高血流动力学中的作用。方法:用SD大鼠制备肝内型(IHPH)、肝前型门脉高压(PHPH)和门腔分流(PCS)3组模型,并以正常鼠作为对照组。每一组实验动物再分成3个亚组:NO生物合成抑制剂L-NMMA组、L-NMMA NO生物合成底物L-精氨酸组以及生理盐水安慰组。血流动力学研究用放射性微球注射技术。结果:IHPH、PHPH和PCS鼠均具有心输出量和内脏血流量增加,平均动脉压、周围血管总阻力和内脏血管阻力降低等高血流动力学特征。L-NMMA能逆转门脉高压鼠和门腔分流鼠的高血流动力学状态,使之恢复至正常鼠的基础水平,但并未达到正常鼠用L-NMMA后的水平。如先给予L-精氨酸,则使L-NMMA对门脉高压鼠和门腔分流鼠的心血管作用消失。结论:门静脉高压症中NO过多产生是高动力循环重要的、但并不是唯一的介质。