瑞芬太尼与芬太尼复合异丙酚用于全身麻醉维持的效果评价

目的 探讨瑞芬太尼与芬太尼复合异丙酚用于全身麻醉维持的效果.方法 将我院择期手术98例患者随机分为瑞芬太尼组和芬太尼组,每组49例.两组麻醉诱导药物相同,瑞芬太尼组静脉持续泵注瑞芬太尼0.1μg/(kg·min),异丙酚0.1 mg/(kg·min)用于麻醉维持.芬太尼组静脉持续泵注芬太尼,异丙酚0.1 mg/(kg·min)用于麻醉维持.观察两组麻醉效果术后并发症.结果 两组患者均能达到手术麻醉要求,两组手术时间、术中失血量、肌松药物用量差异无统计学意义(P>0.05).芬太尼组术后苏醒时间明显长于瑞芬太尼组,芬太尼组VAS疼痛评分明显低于瑞芬太尼组,差异有统计学意义(P<0.05).结论 使用瑞芬太尼或芬太尼复合异丙酚用于全身麻醉维持均能满足手术要求,与芬太尼相比瑞芬太尼术后苏醒快,但术后镇痛效果差.     

瑞芬太尼复合异丙酚或七氟醚用于高龄患者腹腔镜胆囊切除术的临床观察

目的观察比较瑞芬太尼复合异丙酚靶控输注或七氟醚吸入全麻用于高龄患者腹腔镜胆囊切除术的有效性和安全性。方法选择行腹腔镜胆囊切除术的高龄患者60例,ASAⅠ-Ⅲ级,随机分成2组:七氟醚复合瑞芬太尼组(S组)和异丙酚复合瑞芬太尼组(P组),每组30例。P组以瑞芬太尼、异丙酚的血浆靶浓度分别为6ng/ml、3μg/m1行TCI。S组麻醉诱导同P组,气管插管后持续吸入1.5%～2%七氟烷,靶控输注瑞芬太尼(设置参数同P组)。于术毕前5min停止输注异丙酚或吸入七氟醚;缝皮时停止输注瑞芬太尼,于术毕前20min时静脉注射芬太尼0.1mg。分别于麻醉诱导前(T0)、麻醉诱导后(T1)、气管插管时即刻(T2)、手术开始后5min(T3)、30min(T4)和术毕时(T5)记录SBP、DBP、HR等值;采用视觉模拟评分法(VAS)判断术后10min患者疼痛发生情况;观察并记录患者清醒及拔除气管导管时间;观察并记录术后患者躁动的发生情况。结果在T1时,2组患者SBP、DBP和HR均较T0时降低或减慢,差异有统计学意义(P<0.05);组间比较无统计学差异(P>0.05)。S组的清醒时间和拔管时间短于P组,差异有统计学意义(P<0.05);2组患者术后10min的VAS评分比较无统计学差异(P>0.05);术后躁动发生率S组高于P组,差异有统计学意义(P<0.05)。结论异丙酚或七氟醚复合瑞芬太尼麻醉均可安全地用于高龄患者腹腔镜胆囊切除术手术的麻醉,相比之下,七氟醚复合瑞芬太尼的麻醉方法苏醒更迅速,而异丙酚复合瑞芬太尼的麻醉方法苏醒质量优于七氟醚麻醉。     

异丙酚复合瑞芬太尼或芬太尼麻醉应用于腹腔镜胆囊切除术中的疗效比较

目的探讨异丙酚复合瑞芬太尼或芬太尼麻醉应用于腹腔镜胆囊切除术中的疗效比较。方法选择60例ASAⅠ～Ⅱ级择期腹腔镜胆囊切除术患者,随机分为对照组和观察组,对照组麻醉维持采用异丙酚复合芬太尼,观察组麻醉维持采用异丙酚复合瑞芬太尼。结果对照组患者在插管后、切皮后和术中维持MAP、HR和LF/HF均明显高于插管前(P<0.05)。观察组患者各指标在插管后、切皮后和术中维持与插管前比较无明显的变化(P>0.05)。观察组自主呼吸恢复时间、呼之睁眼时间、拔除气管导管时间和定向力恢复时间均明显短于对照组(P<0.05)。对照组发生苏醒期躁动2例,观察组有9例,观察组苏醒期躁动例数明显多于对照组(χ2=5.45,P<0.05)。结论异丙酚瑞芬太尼复合麻醉应用腹腔镜胆囊切除术中,能够抑制气管插管和切皮引起的反应,提供更平稳的血液动力学及更快的麻醉恢复时间,是一种安全、有效的快诱导麻醉方法。     

靶控输注舒芬太尼对腹腔镜胆囊切除术患者内源性一氧化氮及内皮素的影响

目的 探讨靶控输注舒芬太尼对腹腔镜胆囊切除术患者血液动力学,内源性一氧化氮(NO)及内皮素(ET)的影响.方法 50例ASAⅠ～Ⅱ级在全麻下择期行腹腔镜胆囊切除术患者随机分为两组:舒芬太尼组,麻醉维持采用靶控输注舒芬太尼;芬太尼组,麻醉靶控输注芬太尼.术中分别于麻醉前(T1)、气腹前(T2)、气腹后20min(T3)和解除气腹后20min(T4)抽取动脉血行血气分析,同期测定静脉血浆NO及 ET水平.结果 气腹后20min芬太尼组SBP、DBP和PaCO2均较麻醉前明显升高,舒芬太尼组较麻醉前无明显差异,但较芬太尼组明显降低.气腹后20min,两组患者NO、ET均较气腹前明显升高,且芬太尼组明显高于舒芬太尼组.结论 舒芬太尼与芬太尼相比,很好地维持了腹腔镜胆囊切除手术中血浆NO、ET的动态平衡,减小腹腔镜CO2气腹对机体的刺激,维持血流动力学的平衡,改善微循环灌注,减轻腹腔镜对机体的损伤,有利于患者的恢复.     

异丙酚-瑞芬太尼应用于腹腔镜胆囊切除术的麻醉效果观察

目的探讨异丙酚复合瑞芬太尼应用于腹腔镜下胆囊切除术的临床麻醉效果观察。方法选择60例择期进行腹腔镜下胆囊切除手术患者随机分为两组:异丙酚复合瑞芬太尼麻醉组(A组),异氟醚吸入麻醉组(B组),每组30例。A组麻醉维持给予异丙酚复合瑞芬太尼静脉靶注。B组麻醉维持给予异氟醚吸入。观察比较两组的麻醉效果。结果 A组患者术后按指令睁眼恢复情况效果明显优于B组,2组间差异有统计学意义(P<0.05)。结论异丙酚复合瑞芬太尼麻醉在腹腔镜下胆囊切除手术中具有见效快、镇痛作用强、消除快等优势。     

丙泊酚瑞芬太尼复合麻醉对妇科腹腔镜手术中患者内源性一氧化氮及内皮素的影响

目的探讨丙泊酚(异丙酚)瑞芬太尼复合麻醉对妇科腹腔镜手术中内源性一氧化氮(NO)及内皮素(ET)的影响。方法42例ASAⅠ～Ⅱ级在全麻下择期行腹腔镜妇科手术患者随机分为两组:A组,麻醉维持采用咪唑安定与度冷丁;B组,麻醉维持采用异丙酚与瑞芬太尼。术中分别于二氧化碳(CO2)气腹前、气腹后10、30、60min抽取动脉血行血气分析,同期测定静脉血浆NO-2/NO-3及ET水平。结果气腹后30、60min,A组PaCO2、TCO2、NO-2/NO-3及ET水平均明显高于气腹前(P<0.05),B组明显低于A组(P<0.01)。结论腹腔镜CO2气腹可导致机体内源性的NO及ET水平升高,异丙酚可以明显减少内源性NO的氧化代谢,同时降低ET水平。     

瑞芬太尼与芬太尼复合异丙酚用于全身麻醉的效果观察

目的探讨瑞芬太尼与芬太尼复合异丙酚用于全身麻醉观察。方法随机分为瑞芬太尼复合异丙酚用于全身麻醉观察组82例,芬太尼复合异丙酚用于全身麻醉对照组90例,观察两组麻醉对血液动力学影响。结果观察组、对照组MAP、HR,插管前、插管后、手术中、术毕比较P<0.05为差异有统计学意义。结论瑞芬太尼复合异丙酚用于全身麻醉与芬太尼复合异丙酚用于全身麻醉各有优缺点,需根据临床麻醉需要进行联合[1],但瑞芬太尼复合异丙酚用于全身麻醉对血液动力学影响小。     

瑞芬太尼和芬太尼复合异丙酚用于全身麻醉维持的效果分析

目的探讨瑞芬太尼和芬太尼复合异丙酚用于全身麻醉维持的效果。方法 86例行全身麻醉患者,随机分为观察组和对照组,各43例。观察组患者给予瑞芬太尼和芬太尼复合异丙酚用于全身麻醉维持,对照组患者给予芬太尼复合异丙酚全身麻醉维持,观察两组麻醉维持效果。结果两组患者插管前和插管后、手术中和手术后的平均动脉压和心率对比,差异具有统计学意义(P<0.05)。患者未发生不良反应。结论瑞芬太尼和芬太尼复合异丙酚用于全身麻醉维持效果比单纯运用瑞芬太尼或者芬太尼复合异丙酚显著,可以弥补单纯用药的不足,值得在临床推广应用。     

高龄患者静脉应用瑞芬太尼与芬太尼麻醉的临床对比观察

目的观察持续静脉输注瑞芬太尼与芬太尼在高龄患者麻醉中的临床效果。方法择期手术的高龄患者80例,随机分为瑞芬太尼组和芬太尼组,每组40例。分别采用瑞芬太尼和芬太尼为主诱导和麻醉维持,观察全麻诱导前后、气管插管后、手术开始、手术结束及拔管后的血压、心率及血氧饱和度的变化以及术毕停药后患者自主呼吸恢复、意识恢复及拔管时间,并观察术后不良反应如恶心、呕吐、呼吸抑制及肌僵现象的发生。结果两组患者诱导后血压、心率均低于诱导前(P<0.05);瑞芬太尼组患者在气管插管后、切皮时的血压、心率均低于芬太尼组(P<0.05);术后自主呼吸恢复、意识恢复、拔管时间及离开恢复室时间也短于芬太尼组(P<0.05)。结论使用瑞芬太尼麻醉,患者血流动力学更平稳,术后苏醒快,麻醉效果及安全性好,适合用于高龄患者手术麻醉。     

瑞芬太尼和芬太尼对异丙酚静脉麻醉的作用比较

目的对比瑞芬太尼和芬太尼对异丙酚静脉麻醉的作用,比较二者的优劣。方法 80例择期手术患者,ASAⅠ~Ⅱ,分为异丙酚芬太尼(PF组,n=28)靶控输注,异丙酚靶控输注复合瑞芬太尼(PR组,n=32)持续输注全静脉麻醉,异丙酚靶控输注(P组,n=20)。异丙酚初始靶浓度为1mg/L,逐渐增加靶浓度值直至患者意识消失,芬太尼的靶浓度为2μg/L,瑞芬太尼麻醉的诱导和维持分别是0.25~0.5及0.125~0.25μg/(kg min)。术中根据麻醉的需要调整异丙酚、瑞芬太尼输注速度或芬太尼靶浓度值维持所需麻醉深度。观察血流动力学改变,脑电双频指数(BIS),麻醉药用量以及麻醉后恢复情况。结果各组患者诱导后PR组心率明显减慢(P<0.05),收缩压(SBP)、舒张压(DBP)明显降低(P<0.05);PF,PR组气管插管、切皮后SBP及DBP无明显改变,P组则明显升高(P<0.05)。PR,PF组异丙酚麻醉维持用量分别较P组降低38.6%和22.6%(P异丙酚在麻醉中广泛应用,但无明显镇痛作用,单独应用难以满足临床需要,而芬太尼有较好的镇痛作用,但随输注时间增加时一量相关半衰期(context—sensitive halftime)延长,不利术后麻醉恢复,瑞芬太尼(renmifentanil)的时一量相关半衰期不受输注时间长短影响[1]。我们采用输液泵分别输注异丙酚、异丙酚联合芬太尼靶控输注或者异丙酚靶控输注复合瑞芬太尼持续输注全静脉麻醉,观察瑞芬太尼、芬太尼对异丙酚静脉麻醉影响。     

Modulation of prostaglandin biosynthesis by nitric oxide and nitric oxide donors

The biosynthesis and release of nitric oxide (NO) and prostaglandins (PGs) share a number of similarities. Two major forms of nitric-oxide synthase (NOS) and cyclooxygenase (COX) enzymes have been identified to date. Under normal circumstances, the constitutive isoforms of these enzymes (constitutive NOS and COX-1) are found in virtually all organs. Their presence accounts for the regulation of several important physiological effects (e.g. antiplatelet activity, vasodilation, and cytoprotection). On the other hand, in inflammatory setting, the inducible isoforms of these enzymes (inducible NOS and COX-2) are detected in a variety of cells, resulting in the production of large amounts of proinflammatory and cytotoxic NO and PGs. The release of NO and PGs by the inducible isoforms of NOS and COX has been associated with the pathological roles of these mediators in disease states as evidenced by the use of selective inhibitors. An important link between the NOS and COX pathways was made in 1993 by Salvemini and coworkers when they demonstrated that the enhanced release of PGs, which follows inflammatory mechanisms, was nearly entirely driven by NO. Such studies raised the possibility that COX enzymes represent important endogenous "receptor" targets for modulating the multifaceted roles of NO. Since then, numerous papers have been published extending the observation across various cellular systems and animal models of disease. Furthermore, other studies have highlighted the importance of such interaction in physiology as well as in the mechanism of action of drugs such as organic nitrates. More importantly, mechanistic studies of how NO switches on/off the PG/COX pathway have been undertaken and additional pathways through which NO modulates prostaglandin production unraveled. On the other hand, NO donors conjugated with COX inhibitors have recently found new interest in the understanding of NO/COX reciprocal interaction and potential clinical use. The purpose of this article is to cover the advances which have occurred over the years, and in particular, to summarize experimental data that outline how the discovery that NO modulates prostaglandin production has impacted and extended our understanding of these two systems in physiopathological events.     

Feedback inhibition of nitric oxide synthase activity by nitric oxide.

1. A murine macrophage cell line, J774, expressed nitric oxide (NO) synthase activity in response to interferon-gamma (IFN-gamma, 10 u ml-1) plus lipopolysaccharide (LPS, 10 ng ml-1). The enzyme activity was first detectable 6 h after incubation, peaked at 12 h and became undetectable after 48 h. 2. The decline in the NO synthase activity was not due to inhibition by stable substances secreted by the cells into the culture supernatant. 3. The decline in the NO synthase activity was significantly slowed down in cells cultured in a low L-arginine medium or with added haemoglobin, suggesting that NO may be involved in a feedback inhibitory mechanism. 4. The addition of NO generators, S-nitroso-acetyl-penicillamine (SNAP) or S-nitroso-glutathione (GSNO) markedly inhibited the NO synthase activity in a dose-dependent manner. The effect of NO on the enzyme was not due to the inhibition of de novo protein synthesis. 5. SNAP directly inhibited the inducible NO synthase extracted from activated J774 cells, as well as the constitutive NO synthase extracted from the rat brain. 6. The enzyme activity of J774 cells was not restored after the removal of SNAP by gel filtration, suggesting that NO inhibits NO synthase irreversibly.     

Influence of nitric oxide derived from neuronal nitric oxide synthase on glomerular filtration

The neuronal isoform of nitric oxide synthase (nNOS) has been localized to specific regions of the kidney, including the thick ascending limb of the loop of Henle and the macula densa. Because of this discrete localization in the renal cortex, nitric oxide (NO) produced by nNOS has been suggested to play an important role in the regulation of macula densa-mediated arteriole tone and therefore could play an important role in the regulation of whole-kidney glomerular filtration rate (GFR). We hypothesized that selective blockade of nNOS would decrease GFR. Renal hemodynamics were measured before and after acute selective blockade of nNOS by 50 mg/kg 7-nitroindazole (7-NI) in anesthetized rats. Administration of 7-NI had no significant effect on basal blood pressure (from 105 +/- 3 to 101 +/- 2 mm Hg), renal blood flow [from 6.08 +/- 0.39 to 6.31 +/- 0.33 ml/min/gram of kidney weight (gkw)], or total renal vascular resistance (from 18.1 +/- 1.6 to 16.4 +/- 1.0 mm Hg/ml/min/gkw) but decreased GFR by 26% (from 1.36 +/- 0.15 to 1.00 +/- 0.13 ml/min/gkw; p < 0.02), urinary flow rate by 28% (from 24.7 +/- 1.8 to 17.8 +/- 2.2 microl/min; p < 0.05), and sodium excretion by 22% (from 5.55 +/- 0.53 to 4.30 +/- 0.52 microEq/min; p < 0.05). However, fractional sodium excretion was not changed by nNOS inhibition. There were no such changes in vehicle-treated time controls. We conclude that, in the renal cortex, NO produced by nNOS plays an important role in the regulation of whole-kidney GFR and excretion in normal, sodium-replete rats.     

Mitochondrial nitric oxide synthase

Mitochondria produce nitric oxide (NO) through a Ca(2+)-sensitive mitochondrial NO synthase (mtNOS). The NO produced by mtNOS regulates mitochondrial oxygen consumption and transmembrane potential via a reversible reaction with cytochrome c oxidase. The reaction of this NO with superoxide anion yields peroxynitrite, which irreversibly modifies susceptible targets within mitochondria and induces oxidative and/or nitrative stress. In this article, we review the current understanding of the roles of mtNOS as a crucial biochemical regulator of mitochondrial functions and attempt to reconcile apparent discrepancies in the literature on mtNOS.     

Biochemical aspects of nitric oxide

Nitric oxide (NO), a free radical molecule, produced by NO synthase (NOS) in the body exerts a number of pathophysiological actions due to its chemical reactivity. Low amounts of NO (nM) normally produced by constitutive NOS play a critical role in different physiological events such as vasodilation and neurotransmission. Higher amounts of NO ( micro M) locally and spatially produced by inducible NOS during inflammation act as double-edged sword exerting either beneficial or detrimental effects. Recently, new vision on the biological role of NO has been proposed based on the possible cross-talk between constitutive and inducible NOS. Accordingly, normally produced low amounts of NO may be involved in the regulation of NF-kappaB activation and successively the expression of inducible NOS. Under normal conditions NF-kappaB activation is suppressed by low amounts of NO. Under conditions in which massive amounts of NO produced by inducible NOS act detrimentally, NO-elicited down-regulation of NF-kappaB activation is compromised due to the drop in NO at the early phase of inflammation caused by inactivation of constitutive NOS. Any treatment which counterparts the drop in NO, therefore, may present a new approach either in preventing or in treating inflammatory diseases.     

Role of inducible nitric oxide synthase-derived nitric oxide in lipopolysaccharide plus interferon-gamma-induced pulmonary inflammation

Exposure of mice to lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma) increases nitric oxide (NO) production, which is proposed to play a role in the resulting pulmonary damage and inflammation. To determine the role of inducible nitric oxide synthase (iNOS)-induced NO in this lung reaction, the responses of inducible nitric oxide synthase knockout (iNOS KO) versus C57BL/6J wild-type (WT) mice to aspirated LPS + IFN-gamma were compared. Male mice (8-10 weeks) were exposed to LPS (1.2 mg/kg) + IFN-gamma (5000 U/mouse) or saline. At 24 or 72 h postexposure, lungs were lavaged with saline and the acellular fluid from the first bronchoalveolar lavage (BAL) was analyzed for total antioxidant capacity (TAC), lactate dehydrogenase (LDH) activity, albumin, tumor necrosis factor-alpha (TNF-alpha), and macrophage inflammatory protein-2 (MIP-2). The cellular fraction of the total BAL was used to determine alveolar macrophage (AM) and polymorphonuclear leukocyte (PMN) counts, and AM zymosan-stimulated chemiluminescence (AM-CL). Pulmonary responses 24 h postexposure to LPS + IFN-gamma were characterized by significantly decreased TAC, increased BAL AMs and PMNs, LDH, albumin, TNF-alpha, and MIP-2, and enhanced AM-CL to the same extent in both WT and iNOS KO mice. Responses 72 h postexposure were similar; however, significant differences were found between WT and iNOS KO mice. iNOS KO mice demonstrated a greater decline in total antioxidant capacity, greater BAL PMNs, LDH, albumin, TNF-alpha, and MIP-2, and an enhanced AM-CL compared to the WT. These data suggest that the role of iNOS-derived NO in the pulmonary response to LPS + IFN-gamma is anti-inflammatory, and this becomes evident over time.     

Role of inducible nitric oxide synthase-derived nitric oxide in silica-induced pulmonary inflammation and fibrosis

Inhalation of crystalline silica can produce lung inflammation and fibrosis. Inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO) is believed to be involved in silica-induced lung disease. To investigate the role of iNOS-derived NO in this disease, the responses of iNOS knockout (KO) versus C57Bl/6J wild-type (WT) mice to silica were compared. Male mice (8-10 wk old, mean body weight 24.0 g) were anesthetized and exposed, by aspiration, to silica (40 mg/kg) or saline. At 24 h and 42 d postexposure, lungs were lavaged with saline. The first bronchoalveolar lavage (BAL) fluid supernatant was analyzed for lactate dehydrogenase (LDH) activity, levels of albumin, tumor necrosis factor-alpha (TNF-alpha), and macrophage inflammatory protein-2 (MIP-2), as well as total antioxidant capacity (TAC). The cellular fraction of the total BAL was used to determine alveolar macrophage (AM) and polymorphonuclear leukocyte (PMN) counts, and zymosanstimulated AM chemiluminescence (AM-CL). In separate mice, lung histopathological changes were evaluated 42 d postexposure. Acute (24-h) silica exposure decreased AMs, increased PMNs, increased LDH activity and levels of albumin, TNF-alpha, and MIP-2 in BAL fluid, and enhanced AM-CL in both iNOS KO and WT mice. However, iNOS KO mice exhibited less AM activation (defined as increased AM-CL and decreased AM yield) than WT. Furthermore, TAC following acute silica decreased in WT but was maintained in iNOS KO mice. Pulmonary reactions to subchronic (42 d) silica exposure were similar to acute. However, histopathological and BAL fluid indices of lung damage and inflammation, AM activation, and lung hydroxyproline levels were significantly less in iNOS KO compared to WT mice. These results suggest that iNOS-derived NO contributes to the pathogenesis of silica-induced lung disease in this mouse model.     

Co-induction of nitric oxide synthase and cyclo-oxygenase: interactions between nitric oxide and prostanoids.

1. Lipopolysaccharide (LPS) co-induces nitric oxide synthase (iNOS) and cyclo-oxygenase (COX-2) in J774.2 macrophages. Here we have used LPS-activated J774.2 macrophages to investigate the effects of exogenous or endogenous nitric oxide (NO) on COX-2 in both intact and broken cell preparations. NOS activity was assessed by measuring the accumulation of nitrite using the Griess reaction. COX-2 activity was assessed by measuring the formation of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) by radioimmunoassay. Western blot analysis was used to determine the expression of COX-2 protein. We have also investigated whether endogenous NO regulates the activity and/or expression of COX in vivo by measuring NOS and COX activity in the lung and kidney, as well as release of prostanoids from the perfused lung of normal and LPS-treated rats. 2. Incubation of cultured murine macrophages (J774.2 cells) with LPS (1 microgram ml-1) for 24 h caused a time-dependent accumulation of nitrite and 6-keto-PGF1 alpha in the cell culture medium which was first significant after 6 h. The formation of both 6-keto-PGF1 alpha and nitrite elicited by LPS was inhibited by cycloheximide (1 microM) or dexamethasone (1 microM). Western blot analysis showed that J774.2 macrophages contained COX-2 protein after LPS administration, whereas untreated cells contained no COX-2. 3. The accumulation of 6-keto-PGF1 alpha in the medium of LPS-activated J774.2 macrophages was concentration-dependently inhibited by chronic (24 h) exposure to sodium nitroprusside (SNP; 1-1000 microM).(ABSTRACT TRUNCATED AT 250 WORDS)     

Drugs that activate specific nitric oxide sensitive guanylyl cyclase isoforms independent of nitric oxide release

Nitric oxide (NO) releasing drugs have helped patients suffering from angina pectoris for more than a century. In the 1970s NO-sensitive guanylyl cyclase was identified as the target of NO. Since then, three different isoforms of the enzyme have been identified. All NO-releasing drugs act by binding of NO to the prosthetic heme group common to all three isoforms. They thus act all as isoform-unspecific substances. This review addresses recently developed drugs that activate NO-sensitive guanylyl cyclase independent of NO-release. They have great potential in the treatment of angina pectoris, hypertension and erectile dysfunction. The molecular target has been validated by the successful clinical use of NO-releasing drugs for more than a century. At the same time the mode of action of these drugs is entirely new. The development of highly isoform-specific derivatives with distinct pharmacological profiles is now an open possibility with great potential.     

Novel agents targeting nitric oxide

Nitric oxide (NO) is a soluble gas continuously synthesized from the amino acid L-arginine in endothelial cells by the constitutive calcium-calmodulin-dependent enzyme nitric oxide synthase (NOS). Endothelial dysfunction has been identified as a major mechanism involved in all the stages of atherogenesis. Evaluation of endothelial function seems to have a predictive role in humans, and therapeutic interventions improving nitric oxide bioavailability in the vasculature, may improve the long-term outcome in healthy individuals, high-risk subjects or patients with advanced atherosclerosis. Several therapeutic strategies (including statins, angiotensin converting enzyme inhibitors/angiotensin receptors blockers, insulin sensitizers, antioxidant compounds) are now available, targeting both the synthesis and oxidative inactivation of NO in human vasculature, reversing in that way endothelial dysfunction which is enhanced by the release of nitric oxide from the endothelium.