苯那普利对高血压病患者肾功能储备的影响

目的：研究血管紧张素转化酶抑制剂（ACEI）苯那普利对原发性高血压（EH）患者肾功能储备（RFR）的影响。方法：对27例EH患者采血、留尿后，2h内滴注复方氨基酸500mL。1h后再抽血、留尿，测定氨基酸负荷前后的血肌酐、尿肌酐并计算肌酐清除率（Ccr），测定血、尿中一氧化氮（NO）。给予苯那普利10～30mg／d治疗2月，2个月后再次给予氨基酸负荷，测定氨基酸负荷前后的Ccr，血、尿中NO。结果：（1）在未给苯那普利治疗之前，氨基酸负荷后，Ccr明显增加，血、尿中NO明显增加。（2）苯那普利治疗2月后，血压明显下降，血、尿中NO明显增加。（3）苯那普利治疗2月后，再次给予氨基酸负荷时，Ccr增加不明显，血、尿中NO增加不明显。结论：（1）NO在不影响全身血压变化的情况下，可能参与了氨基酸诱导的超滤作用。（2）苯那普利的降压作用可能与NO有关。（3）苯那普利降低了高血压患者的肾功能储备，推测是由于苯那普利治疗后，使得NO水平增加，肾小动脉舒张，从而使得肾小动脉对随后的氨基酸输注缺乏反应性。     

米力农对肠系膜上动脉闭塞性休克兔肠道氧代谢的影响

目的米力农是磷酸二酯酶III抑制剂,许多研究认为能改善休克患者的血流动力学及全身的氧供、氧耗,但对肠道的氧供、氧耗的影响研究甚少。本研究旨在探讨米力农对肠系膜上动脉闭塞性(SMAO)休克兔肠道氧代谢的影响。方法16只健康家兔随机分为对照组和治疗组,经腹分离肠系膜上动脉复制SMAO休克模型。对照组静脉泵入米力农0.1ml·kg-1·min-1,治疗组静脉注入负荷量米力农50μg·kg-1,随后持续泵入米力农0.5ug·kg-1·min-1,液体总量和A组相同。实验期间于夹闭前-1h、松夹后休克时0h、松夹后1h、2h、定时观察MAP,HR,SMAF;测定肠系膜上静脉、颈内动脉血气,并根据公式计算出氧供(DO)2、和氧耗(VO)2。结果松夹后1-2h期间,治疗组较对照组MAP,HR,SMAF,肠道DO2及VO2明显升高(P<0.05或<0.01)。结论米力农能显著增加SMAO休克兔肠系膜上动脉血流量,提高肠道的氧供、氧耗、及全身血压,改善了缺血脏器的血供和氧合状态。     

前列地尔对兔内皮细胞缺氧复氧损伤后抗栓功能的影响

目的：探讨前列地尔（PGE1）对兔内皮细胞缺氧复氧损伤模型的抗栓功能影响。方法对体外培养、并建立兔内皮细胞缺氧复氧损伤的模型进行分组：模型组、低浓度PGE1组、中浓度PGE1组、高浓度PGE1组、正常组。对以上各组培养上清液中一氧化氮（NO）、超氧化物歧化酶（SOD）、丙二醛（MDA）、细胞内血管假性血友病因子（vWF）的含量或表达等进行测量。结果与正常组比较，模型组NO含量、SOD活性、vWF表达均有所下降， MDA含量增加，且差异具有统计学意义（P〈0.05）；而低、中、高浓度PGE1组与模型组比较，其NO含量、SOD活性、vWF表达均有所增加或增强， MDA含量降低，且差异具有统计学意义（P〈0.05）。结论 PGE1对机体缺氧复氧损伤之后的血管内皮细胞抗栓功能具有积极的保护作用。     

阿霉素致大鼠心脏氧化损伤及其机制的研究

目的观察不同剂量阿霉素（ADR）给药后不同时间对大鼠心脏的作用，探讨ADR心脏毒性损伤的可能作用机制。方法60只大鼠随机分为对照组和3个给药组。给药组分别单次腹腔注射5、10和20ms／kg的ADR溶液；对照组给予生理盐水。给药后第1、2和4天每组分别处死5只动物，取心室制备组织匀浆，用硫代巴比妥酸法（TBA）测定丙二醛（MDA）含量，二硫代双硝基苯甲酸法（DTNB）测定总巯基（TSH）和非蛋白巯基（NPSH）含量，Griess试剂法测定一氧化氮（NO）含量。结果随着剂量的增加，给药后第1天心脏组织中NPSH、TSH含量增加；给药后第2天TSH、NO含量增加；给药后第4天MDA、NO含量增加，NPSH含量降低；与对照组比较，20ms／kg组差异有显著性（P〈0．05，P〈0．01）。结论阿霉素致心脏损伤的机制可能与心脏组织中NPSH的耗竭及NO产生过多有关。     

兔脑磷脂对高脂血症家兔调血脂作用

目的观察兔脑磷脂（RBP）对高脂血症家兔血脂紊乱的调节作用。方法18只健康家兔喂饲法制作高脂血症模型,随机分为3组：磷脂高（H）、低（L）剂量组和模型组（M）,另设正常对照组健康家兔6只（C）。采用耳缘静脉推注给药,分别给与兔脑磷脂（RBP）40mg/kg、20mg/kg及生理盐水1ml/kg,连续用药2周,末次给药结束后兔空腹12 h,心脏取血测定各项指标。结果高脂血症模型组兔血胆固醇（Ch）、三酰甘油（TG）、低密度脂蛋白（LDL）、丙二醛（MDA）含量升高（P〈0.05或P〈0.01）,超氧化物歧化酶（SOD）、一氧化氮（NO）、一氧化氮合酶（NOS）含量降低（P〈0.05或P〈0.01）。RBP降低TG、LDL、MDA含量,升高HDL、NO、NOS含量,对SOD升高作用更显著。结论RBP通过抗脂质过氧化作用改善高脂血症家兔血脂紊乱。     

黄蜀葵花总黄酮预处理对脑缺血再灌注损伤的保护作用

目的：研究黄蜀葵花总黄酮（total flavone of Abehnoschl manihot，TFA）对脑缺血再灌注损伤的预适应样保护作用。方法：采用间断静脉推注TFA模拟缺血预适应的方法，分别在大鼠和小鼠大呐中动脉栓塞后再灌模型上，观察脑梗死面积及脑组织和血清中的生化指标的变化。结果：在大鼠大脑中动脉栓塞后再灌模型上，模型组大鼠血清中乳酸脱氢酶（LDH）活性、丙二醛（MDA）和前列腺素E2（PGE2）含量较似手术组明显增高，而TFA（160，80，40，20mg．kg^-1）预处理可明显降低血清中LDH活性、MDA和PGE2含量，同时明显增加血清中一氧化氮合酶（NOS）活性和一氧化氮（N0）含量，TFA（160，80,40，20mg．kg^-1）预处理明显减少脑梗死面积；在小鼠大脑中动脉栓塞后再灌模型上，TFA（200，100，50，25mg／kg）预处理也可明垃减少脑梗死面积并可明显降低血清中LDH和神经元特异性烯醇化酶（NSE）活性以及MDA含量，明显增加血清中NO含量。结论：黄蜀葵花总黄酮预处理对大鼠和小鼠脑缺血再灌注损伤具有预适应样的保护作用。     

亚甲蓝对创伤性休克兔肺损伤的保护作用

目的通过测定创伤性休克兔血浆超氧化物歧化酶（SOD）、丙二醛（MDA）变化以及肺组织病理学改变,评价亚甲蓝（MB）对创伤性休克的疗效及对肺缺血再灌注损伤的保护作用。方法将日本长耳大白兔18只随机分为3,组：对照组、创伤性休克生理盐水复苏组（NS组）和创伤性休克MB复苏组（MB组）,每组6只,记录休克前（T4）、休克末（T2）、复苏末（T3）,复苏后0．5h（T4）、2h（T5）、4h（T6）时间点平均动脉压（MAP）的变化,并测定血浆SOD、MDA,复苏后4h放血处死动物,取肺测定肺叶湿重／干重比,并观察肺形态病理学变化。结果对照组SOD、MDA在各时间点变化不明显。另外2组在MDA水平变化明显升高,且生理盐水复苏组高于MB复苏组（P〈0．05）,SOD明显降低,生理盐水复苏组明显低于MB复苏组（P〈0．05）。肺组织病理学观察显示亚甲蓝对缺血再灌注损伤肺具有保护作用。结论亚甲蓝可能通过抑制氧自由基（ROS）的过度生成,对创伤性休克及其引起的缺血再灌注肺损伤（L／R）产生保护作用。     

挤压伤后丙二醛和一氧化氮的变化

目的 观察挤压伤后脂质过氧化物的终产物－丙二醛（MDA）和一氧化氮（NO）含量变化。方法 复制挤压伤的大鼠模型，测定正常和挤压伤后平均动脉压（MAP）和血浆MDA、NO的含量变化，检测解压2h后心、肝、肾、小肠组织的MDA和NO含量。结果 解压后挤压伤组MAP值均低于对照组，血浆和组织中MDA、NO均高于对照组，并有统计学意义。结论 挤压伤后组织器官损伤与缺血再灌注有关，氧自由基和一氧化氮产生增多是其重要的机制。     

创伤性休克兔血浆一氧化氮的动态变化及亚甲蓝的干预作用

目的 观察创伤性休克兔血浆一氧化氮(nitric oxide,NO)的动态变化及鸟苷酸环化酶抑制药亚甲蓝(Methylene Blue，MB)的干预作用。方法 选用大白兔18只，分为对照组(6只)，生理盐水复苏组(6只)，MB处理组(6只)，生理盐水复苏组及MB处理组记录休克前(T1)、休克末(T2)、复苏末(T3)，复苏后0．5h(T4)、2h(T5)、4h(T6)时间点收缩压(SBP)、舒张压(DBP)、平均动脉压(MAP)及心率(HR)的动态变化，并测定血浆NO的水平，对照组记录相应时间点SBP、DBP、MAP及HR的动态变化，并测定血浆NO的水平。结果兔创伤性休克后，血浆NO水平明显高于休克前，生理盐水复苏组动物复苏后血浆NO进行性增高，于复苏后30分钟达峰值水平，以后逐渐下降，但仍高于休克前；MB处理组动物复苏后血浆NO水平明显降低；对照组各时间点血浆NO无明显变化。结论NO在创伤性休克的病理发展过程中起着重要作用，应用MB可降低血浆NO的水平，有助于创伤性休克的改善。     

丙泊酚在缺血性脑损伤中的保护作用

［摘要］目的在家兔失血性休克模型基础上观察静脉麻醉药丙泊酚对缺血 再灌注损伤后脑的保护作用。方法30只家兔随机分为3组各10只，假手术组仅经股动、静脉穿刺置管，不放血；对照组为失血性休克组；丙泊酚组在失血性休克前10 min腹腔内注射丙泊酚100 mg·kg 1。结果对照组与假手术组比较，休克90 min，再灌注后0.5，2，4 h血清MDA含量明显升高（P＜0.05＝，尤以再灌注后明显（P＜0.01＝; 丙泊酚组在休克90 min时血清MDA含量明显升高（P＜0.05＝；再灌注后0.5，2，4 h血清MDA含量降低，与假手术组比较差异无显著性（P＞0.05）；对照组脑组织MDA含量明显高于其他两组（P＜0.05＝。 结论缺血 再灌注损伤后机体脂质过氧化水平升高，丙泊酚能显著抑制再灌注引起的MDA含量的增高，对缺血 再灌注后的脑损伤有明显的保护作用。     

Effect of Ginsenoside Re on shock

Objective To evaluate the effect of Ginsenoside Re on Shock through different animal models in order to provide preclinical pharmacological experimental data.Methods In superior mesenteric artery occlusion(SMAO)of rats model was established by clamping superior mesenteric artery(SMA)for 2 hours and then reperfusing for another 2 hours.During the whole process mean artery pressure(MAP)and heart rate(HR)were recorded.The blood samples were collected before and 2 hours after clamping respectively,to determine serum GOT,GPT,LDH,GLU,CK,BUN,Cr and NO.Intestine,lung,heart,kidney and liver tissue samples were also collected after reperfusion 2 hours,and(1)protein concentration of bronchia alveolus lung fluid [BALF],(2)HSP70 expression in heart and kidney(3)histology pathology and(4)oxidation injury(MDA and GSH-Px)in above tissues were determined.Hemorrhagic shock(HS)of cats,scald shock model and insulin shock model were also introduced here.Results Ginsenoside Re decreased the morality of SMAO rats and the GOT,GPT,LDH,CK,BUN,NO and Cr level,the GSH-Px activity was increased and MDA content was decreased.The expression of HSP70 in heart and kidney were up-regulated and the protein content in BALF was inhibited after Ginsenoside Re treatment.Ginsenoside Re corrected acidosis induced by HS,and elevated Hb content,reduced serum MDA,LD level.Ginsenoside Re could attenuate liver and lung tissue injury.In scald shock,Ginsenoside Re decreased LDH,CK-MB,a-HBD and Hct of serum and in insulin shock survival time was prolonged.Conclusions Ginsenoside Re showed an anti-shock activity.     

Predisposition of spontaneously hypertensive rats to develop renal injury during nitric oxide synthase inhibition

Chronic nitric oxide (NO) synthase (NOS) inhibition results in renal injury. Hypertension is an important risk factor for renal injury. We studied the influence of preexistent hypertension on the sensitivity for renal injury induced by chronic NOS inhibition in rats. Spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were treated with 3, 10, 30 and 100 mg/l Nomega-nitro-L-arginine (L-NNA) until death. Systolic blood pressure and proteinuria were measured regularly and compared with time-control measurements in untreated SHR and WKY. In WKY, 3 and 10 mg/l L-NNA did not affect systolic blood pressure, while 30 and 100 mg/l L-NNA resulted in an increase in systolic blood pressure after 12 and 4 weeks, respectively. In contrast in SHR, every dose of L-NNA resulted in an increase in systolic blood pressure after 2 weeks. In WKY, 3 and 10 mg/l L-NNA did not affect proteinuria or survival, while 30 and 100 mg/l L-NNA resulted in an increase in proteinuria after 30 and 9 weeks, and a median survival of 36 and 12 weeks, respectively. In SHR, 3, 10, 30 and 100 mg/l L-NNA resulted in an increase in proteinuria after 30, 12, 3 and 3 weeks, and a median survival of 41, 20, 5 and 3 weeks, respectively. Thus, at every dose of the inhibitor, chronic NOS inhibition resulted in far earlier increases in systolic blood pressure and proteinuria and a marked increase in mortality in SHR as compared to WKY. Indeed, a very low dosage of L-NNA that caused no harm in WKY was followed by marked increases in proteinuria and blood pressure and decreased survival in SHR. Hypertension strongly increases the vulnerability to cardiovascular risk factors that compromise the NO-system.     

Enhancement of noradrenergic constriction of large coronary arteries by inhibition of nitric oxide synthesis in anaesthetized dogs.

1. Coronary vascular responses to bilateral carotid occlusion (BCO) and the intravenous infusion of tyramine (Tyr, 20 micrograms kg-1 min-1) and noradrenaline (NA, 0.5 microgram kg-1 min-1) were examined after bilateral vagotomy and antagonism of beta-adrenoceptors. BCO, Tyr and NA decreased large coronary artery diameter and increased mean coronary resistance and systemic arterial pressure without affecting heart rate. 2. Inhibition of nitric oxide (NO) synthase with NG-nitro-L-arginine (L-NNA, 5 and 15 mg kg-1) significantly increased mean arterial pressure and decreased heart rate and large coronary artery diameter. Mean coronary resistance was unaffected by either dose of L-NNA. L-NNA significantly reduced depressor and coronary vasodilator responses to the endothelium-dependent vasodilator acetylcholine (ACh, 10 micrograms kg-1, i.v.). Systemic and coronary vasodilator responses to sodium nitroprusside (SNP, 5 micrograms kg-1) were unaffected by L-NNA with the exception that the dilatation of the large coronary artery was significantly enhanced by the higher dose. 3. L-NNA significantly enhanced constriction of the large coronary arteries caused by BCO, Tyr and NA but did not affect the increases in mean coronary resistance or systemic arterial pressure. 4. Inhibition of NO synthesis enhances adrenergic constriction of large coronary arteries caused by both neuronally released and exogenous noradrenaline. In contrast, L-NNA did not affect adrenergic constriction of coronary or systemic resistance vessels. Endothelium-derived NO may play an important role in the modulation of noradrenergic vasoconstriction in coronary conductance arteries.     

6-[4-(4′-吡啶)氨基苯]-4,5-二氢-3(2H)哒嗪酮抗兔和大鼠失血性休克效应及初步机理

目的　研究新型钙增敏强心剂 6 [4 (4′ 吡啶 )氨基苯 ] 4 ,5 二氢 3(2H)哒嗪酮 (MCI 15 4 )抗失血性休克效应并探讨其初步机理。方法　以改良Wigger法 ,即股动脉放血并维持血压 5 .33kPa 2h建立失血性休克动物模型 ,观察MCI 15 4对失血性休克大鼠 12、2 4和 4 8h存活率的影响 ;以彩色频谱多普勒观察MCI 15 4对失血性休克家兔心脏射血分数、每搏输出量及肝动脉、肠系膜上动脉、右肾动脉平均血流量和血流阻力指数的影响。结果　MCI 15 4组休克大鼠 12、2 4和 4 8h存活率分别为 17/ 2 0、15 / 2 0和13/ 2 0 ,明显高于生理盐水组的 11/ 2 0、8/ 2 0、4 / 2 0 ;MCI 15 4治疗后 2h ,能显著降低休克家兔肝、肾动脉血流阻力指数 ;治疗后 4h能明显增加休克家兔心脏射血分数、每搏输出量及肠系膜上动脉、肾动脉血流量 ,显著降低肝动脉血流阻力指数。结论　MCI 15 4有较满意的抗失血性休克效应 ,其机理可能与增强休克动物心脏功能和增加主要器官血流量有关。     

6-［4-(4′-吡啶)氨基苯］-4，5-二氢-3(2H)哒嗪酮抗兔和大鼠失血性休克效应及初步机理

目的 研究新型钙增敏强心剂6-［4-(4′-吡啶)氨基苯］-4，5-二氢-3(2H)哒嗪酮(MCI-154)抗失血性休克效应并探讨其初步机理。方法 以改良Wigger法，即股动脉放血并维持血压5.33 kPa 2 h建立失血性休克动物模型，观察MCI-154对失血性休克大鼠12、24和48 h存活率的影响；以彩色频谱多普勒观察MCI-154对失血性休克家兔心脏射血分数、每搏输出量及肝动脉、肠系膜上动脉、右肾动脉平均血流量和血流阻力指数的影响。结果 MCI-154组休克大鼠12、24和48 h存活率分别为17/20、15/20和13/20，明显高于生理盐水组的11/20、8/20、4/20；MCI-154治疗后2 h，能显著降低休克家兔肝、肾动脉血流阻力指数；治疗后4 h能明显增加休克家兔心脏射血分数、每搏输出量及肠系膜上动脉、肾动脉血流量，显著降低肝动脉血流阻力指数。结论 MCI-154有较满意的抗失血性休克效应，其机理可能与增强休克动物心脏功能和增加主要器官血流量有关。     

Analysis of pulmonary vascular response to acute alveolar hypoxic challenge in young rabbits subjected to chronic hypoxia from birth

Chronic alveolar hypoxia induces vascular changes leading to pulmonary hypertension. We investigated the role of nitric oxide synthase (NOS) on basal pulmonary artery pressure (PAP) and on changes in PAP arising from an acute alveolar hypoxic challenge (AAHC) in normoxic and chronically hypoxic young rabbits. The chronically hypoxic rabbits were raised from birth in a chamber containing a (10% O2 + 90% N2) gas mixture, whereas the normoxic rabbits were kept in room air. The age of the animals at the time of study (approximately 38 days) was not significantly different between the 2 groups of rabbits. The in vivo PAP was measured using a right heart catheterization technique while the rabbits were spontaneously breathing either a hyperoxic or a hypoxic gas. In the chronically hypoxic group, the AAHC (hypoxic gas) produced a modest increase in PAP. However, after intravenous administration of (100 mg/kg) of the NOS inhibitor, L-NAME (N-nitro-L-arginine methyl ester), a marked increase in PAP was observed when these rabbits were rechallenged with the AAHC. In contrast, in the normoxic rabbits, the AAHC produced only a small increase in PAP, even after pretreatment with L-NAME. In both groups of rabbits, L-NAME led to a significant rise in basal PAP. Using Western blot analysis, we found endothelial NOS (eNOS) protein expression to be significantly increased in pulmonary artery and right ventricular myocardium of the chronically hypoxic rabbits. These results suggest that release of nitric oxide is involved in regulating basal PAP and in modulating the hypoxia-induced pulmonary vasoconstrictor response in immature animals. Moreover, eNOS appears to undergo up-regulation as a consequence of chronic hypoxia.     

Effects of S-ethylisothiourea, a potent inhibitor of nitric oxide synthase, alone or in combination with a nitric oxide donor in splanchnic artery occlusion shock.

1. The aim of this study was to compare the effects of an intravenous infusion of a potent and non selective nitric oxide synthase inhibitor S-ethylisothiourea (Ethyl-TU) with that of a nitric oxide (NO) donor on the pathological sequelae associated with splanchnic artery occlusion (SAO) shock. In addition the effects of the combination of these two treatments were also investigated. 2. SAO shock was induced in anaesthetized rats by clamping splanchnic arteries for 45 min. Sham operated animals were used as controls. Survival time, white blood cell (WBC) count, mean arterial blood pressure, myeloperoxidase activity (MPO; studied as a quantitative means to evaluate neutrophil accumulation) and the responsiveness of aortic rings to acetylcholine (ACh, 10 nM-10 microM) and to phenylephrine (PE, 1 nM-10 microM) were studied. 3. SAO shocked rats had a decreased survival rate (0% survival 2 h after the release of occlusion) and survival time (76 +/- 10 min), increased MPO activity in the ileum (3.39 +/- 0.8 u x 10(-3) g-1 tissue), a marked leukopenia and a profound hypotension. In addition aortic rings from shocked rats showed a marked hyporeactivity to PE and reduced responsiveness to ACh. Endothelium denuded aortic rings had also a marked hyporeactivity to PE. 4. In vivo administration of Ethyl-TU (0.1 mg kg-1 h-1, beginning 1 min after the onset of reperfusion) significantly increased survival time and rate, improved mean arterial blood pressure, restored the responsiveness to PE, but did not change MPO activity, leukopenia or the impairment in the responsiveness of aortic rings to ACh. Addition of Ethyl-TU (2 microM) to endothelium denuded aortic rings in vitro, restored the marked hyporeactivity to PE. Administration of the NO donor C87-3754 (0.75 mg kg-1 h-1, beginning 1 min after the onset of reperfusion) slightly increased survival time and reduced MPO activity and leukopenia, but did not change survival rate and mean arterial blood pressure. In addition C87-3754 restored the responsiveness of aortic rings to ACh to control values, but did not modify the hyporeactivity to PE. The combination of these two interventions produced a higher degree of protection than either Ethyl-TU or C87-3754 alone. In fact, co-administration of Ethyl-TU plus C87-3754 completely prevented mortality, reduced MPO activity, attenuated leukopenia and the profound hypotension and restored the impaired responsiveness of aortic rings to PE and ACh. 5. Our study suggests that treatment with a nitric oxide synthase inhibitor combined with an NO donor may be a new therapeutic approach to the treatment of splanchnic artery occlusion shock.     

N-nitro L-arginine causes coronary vasoconstriction and inhibits endothelium-dependent vasodilatation in anaesthetized greyhounds.

1. The effect of N-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide biosynthesis, on large coronary artery diameter and coronary blood flow was examined in anaesthetized greyhounds. The effects of L-NNA on the coronary vascular responses to acetylcholine (ACh), glyceryl trinitrate (GTN) and 5-hydroxytryptamine (5-HT) were also assessed. 2. L-NNA (5 mg kg-1), infused into the left circumflex coronary artery, increased systemic mean arterial pressure and decreased the external diameter of the artery. Infusion of L-NNA decreased coronary blood flow in 5 of the 7 dogs tested and increased mean coronary resistance but neither of these effects was statistically significant. There was no change in heart rate. 3. Intra-arterial injection of both ACh (0.01-0.05 micrograms kg-1) and GTN (0.1-0.5 micrograms kg-1) increased large coronary artery diameter and coronary blood flow. Coronary vascular responses to the endothelium-dependent vasodilator ACh were significantly reduced by L-NNA, whereas the responses to the endothelium-independent vasodilator GTN were not significantly affected. 4. 5-HT (0.1 microgram kg-1, injected into the left circumflex coronary artery) decreased coronary artery diameter but increased coronary blood flow. After the administration of L-NNA the 5-HT-induced dilatation of the coronary resistance vessels was significantly attenuated whereas the constriction of the circumflex coronary artery was increased in 3 out of 3 dogs in which diameter could be measured, although the latter effect was not statistically significant. 5. These data indicate that L-NNA causes coronary and systemic vasoconstriction and selectively inhibits endothelium-dependent vasodilatation in the coronary circulation of the anaesthetized greyhound.(ABSTRACT TRUNCATED AT 250 WORDS)     

Shock induction by arterial hypoperfusion of the gut involves synergistic interactions between the peripheral enkephalin and nitric oxide systems

To determine whether critical splanchnic artery hypoperfusion can provoke systemic shock and to identify the roles of the peripheral opioid and nitric oxide (NO) systems in this process, various degrees of superior mesenteric artery hypoperfusion (SMA-H) were produced in anesthetized adult rabbits (n=40), and hemodynamic and metabolic indices were measured. Metabolic acidosis and irreversible hypodynamic shock occurred with SMA-H at levels representing 25-20% of mean baseline SMA blood flow. In 112 other rabbits subjected to SMA-H at 20% (SMA-H20%), we studied plasma NO and enkephalin (ENK) levels, cardiovascular reactivity to selected physiological agonists, effects of ENKs on plasma NO levels, and effects of peripheral opioid receptor blockade and inducible NO synthase (iNOS) inhibition. SMA-H20% progressively increased systemic blood levels of NO and ENKs. Exogenous ENK administration accentuated SMA-H20%-induced increases in plasma NO levels, and their cardiovascular depressing effects were significantly greater when they were administered during SMA-H20% (vs. administration under baseline conditions). Selective blockade of cardiovascular delta-opioid receptors improved hemodynamics, prevented shock irreversibility and reduced plasma NO levels; similar effects were obtained by selective iNOS inhibition. These findings demonstrate that critical arterial hypoperfusion of the gut can induce hypodynamic systemic shock through ENK-induced hyperactivation of cardiovascular delta-opioid receptors, which leads to increased plasma levels of NO related in part to increased iNOS activity. Since pronounced splanchnic artery hypoperfusion occurs in all advanced systemic shock states, selective delta-opioid receptor antagonists and/or iNOS inhibitors may prove to be useful in improving shock hemodynamics and metabolic derangements and/or preventing progression toward irreversibility.     

Combination therapy with inhaled nitric oxide and intravenous dobutamine during pulmonary hypertension in the rabbit

Combination therapy with an intravenous inovasodilator and inhaled nitric oxide (NO) may be appropriate in patients with pulmonary hypertension and associated right ventricular failure. We examined whether dobutamine and inhaled NO would have additive pulmonary vasodilator effects in experimental pulmonary hypertension. Pulmonary hypertension was produced in anesthetized, mechanically ventilated rabbits by infusion of U46619, a thromboxane analogue. Dobutamine was administered in increasing doses (2.5-20 microg/kg/min) with and without inhaled NO (40 ppm). Dobutamine produced dose-dependent decreases in pulmonary vascular resistance (PVR) and mean arterial pressure (MAP) and increases in cardiac output (CO). Inhaled NO alone decreased pulmonary artery pressure (PAP) and PVR with no effect on MAP or CO. The effects of dobutamine and inhaled NO were additive, so that at each dose of dobutamine, inhaled NO decreased PAP and PVR with no effect on systemic hemodynamics. This study suggests that the combination of dobutamine and inhaled NO should produce additive pulmonary vasodilation in patients with pulmonary hypertension and associated right ventricular dysfunction.