环氧化酶及5-脂氧化酶对肾炎模型中肾小球iNOS表达的影响

目的;研究花生四烯酸（ＡＡ）环氧化酶产物及５－脂氧化酶产物对大鼠加速性肾毒性血清性肾炎（ＮＳＮ）中肾小球诱生型一氧化氮合成酶表达的影响。方法：制备ＮＳＮ大鼠模型后,应用消炎痛抑制ＡＡ环氧化酶,应用ＭＫ－０９５１抑制ＡＡ的５－脂氧化酶,观察对肾小球ｉＮＯＳ表达的影响。结果;在ＮＳＮ大鼠,应用消炎痛抑制环氧化酶,可减少肾小球合成的前列腺素（ＰＧ）Ｆ２及血栓素（ＴＸ）Ｂ２,使肾小球ｉＮＯＳ表达增强,尿亚     

硝酸甘油对哮喘患者一氧化氮内皮素的影响及机制

目的　了解哮喘患者肺泡巨噬细胞（ＡＭ） 、支气管上皮细胞（ＢＥＣ） 源性一氧化氮（ＮＯ）、内皮素（ＥＴ）的分泌状态及硝酸甘油（ＮＴＧ）对哮喘患者ＡＭ、ＢＥＣ产生ＮＯ、ＥＴ的影响及机制。方法　分离纯化了１５ 例轻、中度哮喘发作期患者、７ 名健康受试者ＡＭ、ＢＥＣ,并分为哮喘未干预组、哮喘ＮＴＧ干预组和健康对照组,用放射免疫法和镀铜镉还原法分别测定ＡＭ、ＢＥＣ培养４８ 小时上清液中ＥＴ、ＮＯ·２／ＮＯ·３ 浓度,用原位杂交的方法检测ＡＭ、ＢＥＣｉＮＯＳｍＲＮＡ、ＥＴｍＲＮＡ 的表达。结果　（１） 健康受试者ＡＭ、ＢＥＣ分泌少量ＮＯ和ＥＴ及少量ｉＮＯＳｍＲＮＡ 、ＥＴｍＲＮＡ表达;（２）哮喘患者ＡＭ、ＢＥＣ源性ＮＯ、ＥＴ水平及ＡＭ、ＢＥＣｉＮＯＳｍＲＮＡ、ＥＴｍＲＮＡ表达与各组比较差异有显著性（ Ｐ均＜ ０－０５）;（３）ＮＴＧ 促进哮喘患者ＡＭ、ＢＥＣ源性ＮＯ产生（ Ｐ均＜０－０５）,明显抑制ＥＴ产生和ＥＴｍＲＮＡ 的表达,与对照组比较差异均无显著性（ Ｐ均＞ ０－０５） ,ＮＴＧ同时抑制哮喘患者ＡＭ、ＢＥＣｉＮＯＳｍＲＮＡ的表达,与健康对照组、哮喘未干预组比较差异有显著性（Ｐ均＜０－０５） ;（４） 除哮喘ＮＴＧ     

糖尿病早期肾脏内皮素的改变

目的：观察内皮素（ＥＴ）是否参与糖尿病早期肾脏高灌注、高滤过的形成。 方法：应用廓清试验观察４周糖尿病大鼠肾血流量（ＲＰＦ）和肾小球滤过率（ＧＦＲ）；应用半定量逆转录聚合酶链式反应（ＲＴ－ＰＣＲ）分别观察肾皮、髓质ＥＴ－１、ＥＴ－３、ＥＴ－Ａ受体及诱生型一氧化氮合成酶（ｉＮＯＳ）的基因表达情况。 结果：４周糖尿病大鼠存在ＲＰＦ、ＧＲＦ升高；肾脏皮质ＥＴ－１、ＥＴ－Ａ受体表达增加。 结论：内皮素可能     

应用ONE－TOUCHⅡ型血糖监测仪测定毛细血管全血糖

应用ＯＮＥ－ＴＯＵＣＨⅡ型血糖仪测定毛细血管全血糖（ＣＢＧ）１２６４例次，并与ＢｅｃｋｎｉａｎＣｘ４自动生比分折仪测定静脉血浆糖（ＶＰＧ）比较。结果表明，ＶＰＧ较ＣＢＧ高１０．２±０．４％，且两者明显相关。当ＶＰＧ在４．４ｍｍｏｌ／Ｌ以上时，ＶＰＧ＞ＣＢＧ，血糖愈高，差别愈大；而在４．４ｍｍｏｌ／Ｌ以下时，ＶＰＧ＜ＣＢＧ。进餐（或葡萄糖）后３０分钟、６０分钟，ＶＰＧ与ＣＢＧ相对差最小，至１２０分钟、１８０分钟时恢复到空腹水平。误差表格分析显示，所有测定值的９０．２％，７．５％处于Ａ、Ｂ区，仅２．３％处于↑Ｄ区。贫血时ＣＢＧ测值偏高。说明ＯＮＥ－ＴＯＵＣＨⅡ血糖仪测ＣＢＧ快速、简便、准确，故不仅用于糖尿病患者血糖自我监测，且可用于糖尿病的筛选、普查。     

血清谷氨酰转肽酶在慢性乙型肝炎诊断中的价值

目的 探讨血清γ－谷氨酰转肽酶（ＧＧＴ）在慢性乙型肝炎（ＣＨＢ）不同程度肝脏病理损害中的变化规律及其在ＣＨＢ诊断中的价值。方法 测定２２１例ＣＨＢ患者血清ＡＬＴ、ＡＳＴ及ＧＧＴ水平，同时行肝活体组织检查，对肝组织进行炎症分级和纤维分期。分析ＡＬＴ、ＡＳＴ、ＧＧＴ与ＣＨＢ之间的关系。结果 （１）病理轻度和重度ＣＨＢ的ＧＧＴ正常率分别为９０．４％和１２３％（Ｐ＜００１）；（２）临床诊断为轻度、而病理诊断分别为轻、中、重度的ＣＨＢ患者中，ＧＧＴ依次递升（Ｐ＜０．０１）；（３）在活动性ＣＨＢＳ患者中，ＧＧＴ随ＡＬＴ的升高而升高，存在着正向线性相关（ｒ＝０．４６４；Ｐ＜０．００１）。在保肝治疗中，ＧＧＴ、ＡＬＴ较快降至正常的为轻度ＣＨＢ；ＧＧＴ持续在一个较高水平波动，而ＡＬＴ下降，甚至呈ＡＬＴ－ＧＧＴ分离的多分别为中或重度ＣＨＢ。结论ＧＧＴ是提高ＣＨＢ临床与病理诊断符会率的一个有价值的参考指标。     

血栓素及白三烯参与肾炎模型急性肾功能减退的机理研究

在抗Ｔｈｙ１．１抗体所玫的大鼠系膜增殖性肾炎模型中，研究了白细胞衍生的ＴＸ及ＬＴ参与急性肾功能减迟的肾小球血液动力学机理。在肾炎鼠ｋｆ，ＧＦＲ及ＲＢＦ的急性降低伴有肾小球白细胞计数的升高及肾小球ＴＸＢ２，ＬＴＢ４的合成增多。除去白细胞可抑制ＴＸＢ２，ＬＴＢ４的合成外，能完全防止ＧＦＲ及ＲＢＦ的降低。合用ＴＸ合成酶抑制剂及花生四烯酸５－脂氧化酶抑制剂也防止了ＧＦＲ及ＲＢＦ的降低，分别抑制ＴＸ合成酶或５－脂氧化酶仅可部分防止ＧＦＲ及ＲＢＦ的降低。ＴＸ受体拮抗剂或５－脂氧化酶抑制剂可防止入球小动脉阻力的升高及ｋｆ的减少。结果表明，浸润于肾小球的白细胞所衍生的ＴＸ，ＬＴ通过收缩入球小动脉、减少ｋｆ，而参与系膜增殖性肾炎模型的急性肾功能减退。     

不同基因区反义寡核苷酸抑制乙型肝炎病毒基因表达的比较

目的探讨反义寡核苷酸（ＡＳＯＮ）特异性抗病毒作用。方法在ＨｅｐＧ２２．２．１５细胞中观察了４段１６聚针对乙型肝炎病毒（ＨＢＶ）基因不同功能区的ＡＳＯＮ对病毒复制的抑制作用。结果ＡＳＯＮ能显著抑制ＨＢＶ基因的抗原表达（Ｐ＜０．００１），在Ｓ基因区设计的ＡＳＯＮ对ＨＢｓＡｇ的抑制作用明显优于Ｃ基因区的ＡＳＯＮ（Ｐ＜０．０５）。反之，在Ｃ基因区设计的ＡＳＯＮ对ＨＢｅＡｇ的抑制作用又明显优于Ｓ和Ｐｒｅ－Ｓ２基因区的ＡＳＯＮ（Ｐ＜０．０１）。４段ＡＳＯＮ的联合用药并不能增强其对ＨＢＶ的抑制作用。结论ＡＳＯＮ可能成为一种有开发潜力的抗病毒药物。     

叔丁基痉基茴香醚对小鼠醋氨酚中毒性肝损伤的操作作用

目的：采用小鼠醋氨酚中毒性肝损伤模型探讨２（３）－叔丁基－４－羟基茴香醚（ＢＨＡ）对肝脏的保护作用。方法：通过腹腔注射醋氨酚制备小鼠肝损伤模型,测定小鼠血清丙氨酸转氨酶（ＡＬＴ）活笥和肝匀浆液中的丙二醛（ＭＤＡ）含量、超氧化的岐化酶（ＳＯＤ）活性及谷胱甘肽（ＧＳＨ）含量。结果：０．２％及０．５％的ＢＨＡ都能显著对抗醋氨酚所致小鼠肝损伤的血清ＡＬＴ活性升高,肝组织ＭＤＡ含量升高、ＳＯＤ活性降低及还原     

参黄冲剂对慢性肝病患者的抗脂质过氧化作用

以中药验方提取制成参黄冲剂，并与维生素Ｃ、Ｅ对照治疗慢性活动性乙型肝炎（ＣＡＨ）１２６例，肝炎后肝硬化（ＰＨＬＣ）６０例，酒精性肝病（ＡＨＰ）３２例；比较治疗前、后慢性肝病血清ＡＬＴ、ＢｉＬ、ｒ－ＧＴ、血清脂质过氧化物（ＬＰＯ）、红细胞过氧化物歧化酶（ＳＯＤ）、血清Ⅲ型前胶（ＰＣⅢ）等的变化。结果：ＣＡＨ和ＰＨＬＣ治疗组ＡＬＴ、ＢｉＬ和ｒ－ＧＴ均有改善（Ｐ〈０．０１或Ｐ〈０．０５），ＬＰＯ降低接近     

糖基化产物对正常大鼠尿蛋白排泄和肾脏结构的影响

目的为探讨糖基化产物对正常肾脏的特异性损害作用。方法正常大鼠静脉注射体外制备的糖基化血清蛋白（ＧＳＰ），为期２个月，观察ＧＳＰ对大鼠尿蛋白排泄、肾皮质糖基化产物和肾脏形态的影响。结果接受ＧＳＰ的大鼠血清和肾组织中糖基化终产物（ＡＧＥｓ）水平、肾小球硝基四氮唑蓝（ＮＢＴ）染色强度、尿蛋白排泄量和尿量均明显高于对照组。光学和电子显微镜观察显示，给予ＧＳＰ的大鼠肾小球体积明显增大，肾小球系膜区扩大伴有细胞外基质增加，ＰＡＳ阳性物质沉着增多和肾小球基底膜节段性增厚。结论糖基化产物能引起类似糖尿病肾病的肾脏损害。     

Platelet-activating factor stimulates eicosanoid production in cultured feline tracheal explants.

Eicosanoids have been shown to be major mediators of airway inflammation. Platelet-activating factor (PAF), a potent bronchoconstrictor and stimulator of respiratory mucous secretion, may mediate some of its effects via eicosanoid production. To explore eicosanoid generation by cultured feline tracheal explants, eicosanoids were measured following PAF stimulation. After labeling the explants with [3H]arachidonic acid, supernatant from control and PAF treated explants was fractionated by reverse phase high-performance liquid chromatography (HPLC). The resulting elution pattern suggested the release of arachidonic acid (AA), 15-hydroxyeicosatetraenoic acid (HETE), leukotriene (LT)B4, C4, prostaglandin (PG) D2/E2/F2 alpha, and 6-keto-PGF1 alpha. Radioimmunoassay (RIA) following HPLC resolution confirmed that PAF induced a significantly increased release of peptido-leukotrienes, PGD2, PGE2, PGF2 alpha, LTB4, and 5-HETE, as well as thromboxane (TX) B2. The most remarkable increase was LTC4/D4/E4 (15 x control) and PGD2 (4 x control). The PAF antagonist Ro 19-3704 had an inhibitory effect on the PAF-stimulated release of peptido-leukotrienes. We conclude that PAF stimulates the production of a variety of lipoxygenase and cyclooxygenase pathway metabolites in feline airways.     

Lipoxygenase products regulate nitric oxide and inducible nitric oxide synthase production in interleukin-1beta stimulated vascular smooth muscle cells.

In cultured vascular smooth muscle cells (VSMCs), interleukin-1beta (IL-1beta) stimulates inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production. IL-1beta also activates phospholipase A2 (PLA2), and induces lipoxygenase (LOX) and cyclooxygenase-2 (COX-2). The present study investigated whether these metabolites are involved in the regulation of IL-1beta-induced NO production and iNOS expression. Pretreatment with ONO-RS-082, the secretory PLA2 (sPLA2) inhibitor, at 1 to 10 micromol/l reduced IL-1beta-stimulated nitrite production and iNOS expression. Nordihydroguaiaretic acid (NDGA, 1 to 10 micromol/l), the LOX inhibitor, also reduced IL-1beta (10 ng/ml)-stimulated nitrite production and iNOS expression in a dose-dependent manner. Exogenous 12(S)-hydroxyeicosatetraenoic acids (HETE) enhanced the IL-1beta-stimulated nitrite production and iNOS expression. On the other hand, the COX inhibitors, indomethacin and NS-398, had little effect on nitrite production or iNOS expression. These results suggest that LOX products play important roles in the regulation of stimulus-induced NO production in VSMCs.     

Long-term fenofibrate treatment impairs endothelium-dependent dilation to acetylcholine by altering the cyclooxygenase pathway

OBJECTIVE: Experimental studies and opinion articles emphasize that cardiovascular alterations associated with ageing can be improved by the long-term use of fenofibrates. We analyzed the effect of fenofibrate treatment on the acetylcholine-induced relaxation in rat aorta and the participation of nitric oxide (NO) and cyclooxygenase (COX)-derived factors in this effect. METHODS: Acetylcholine relaxation in untreated and 6-week fenofibrate-treated Wistar rats was analyzed in the absence and presence of the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), the specific inducible NO (iNOS) synthase inhibitor 1400W, the nonspecific COX inhibitor indomethacin, the specific COX-2 inhibitor NS-398, the specific thromboxane receptor antagonist SQ-29548, the thromboxane synthesis inhibitor furegrelate, the prostacyclin synthesis inhibitor tranylcypromine, or the 20-HETES synthesis inhibitor formamidine. eNOS, iNOS, COX-1, and COX-2 expression was studied by Western blotting. In addition, production of prostaglandin F(2alpha) (PGF(2alpha)), thromboxane A(2) (TxA(2)), prostaglandin E(2) (PGE(2)), isoprostanes, and prostacyclin (PGI(2)) was also measured. RESULTS: Fenofibrate treatment reduced acetylcholine relaxation. Indomethacin, NS-398, and tranylcypromine decreased acetylcholine relaxation in untreated rats but enhanced relaxation in treated rats. SQ-29548 increased acetylcholine responses in segments from treated rats but not in segments from untreated rats. L-NAME decreased vasodilator response to acetylcholine in both groups while furegrelate, NS-398, 1400W, and formamidine did not affect acetylcholine responses in either group. eNOS and COX-2 expression was higher in aorta from treated rats while COX-1 and iNOS remained unmodified. Basal and acetylcholine-stimulated NO and PGE(2) release were increased, and that of PGI(2) decreased in treated rats. TxA(2) release was similar, but PGF(2alpha) release was undetectable in both groups. CONCLUSIONS: Although it increases NO production through increases in eNOS expression, fenofibrate treatment induces endothelial dysfunction. This effect seems to be mediated by decreased PGI(2) and increased PGE(2) release, and it may help to explain the rise in thromboembolic events observed after long-term fenofibrate treatment in humans.     

Inhibition by methylprednisolone of zymosan-induced leukotriene synthesis in alveolar macrophages

Alveolar-macrophage-derived 5-lipoxygenase metabolites of arachidonic acid (AA) are thought to be important mediators of lung inflammation and injury. Inhibition of AA metabolism may be an important anti-inflammatory mechanism of glucocorticoid (GC) action. In the present study, we have examined the effect of methylprednisolone (MP) on leukotriene (LT) B4 and LTC4 synthesis by cultured rat alveolar macrophages (AMs) stimulated with the proinflammatory particle zymosan. Zymosan stimulation resulted in the formation of LTB4 greater than thromboxane B2 (TxB2) greater than LTC4 as assessed by both high performance liquid chromatography and radioimmunoassay. Sixteen hours of pretreatment with 1 microM MP maximally inhibited synthesis of TxB2 by 76 +/- 4%, LTB4 by 83 +/- 3%, and LTC4 by 91 +/- 3%. The inhibition of eicosanoids was specific, as the sex hormones progesterone, testosterone, and beta-estradiol had no consistent effect. Inhibition was dose-dependent, with 50% inhibition of synthesis occurring at 10(-7) M for TxB2, but at 10(-8) M for both LTB4 and LTC4. Pretreatment with MP for only 1 h inhibited LTC4 production (42 +/- 3%) to a greater extent than either TxB2 (25 +/- 1%) or LTB4 (14 +/- 7%). These data indicate that MP significantly and substantially inhibits zymosan-induced LTB4 and LTC4 synthesis. Furthermore, the greater degree, greater potency, and faster onset of action for MP inhibition of LT synthesis than of TxB2 synthesis suggest the possibility that MP may exert postphospholipase effect(s) on LT synthesis. These results support the possibility that modulation of AM arachidonate metabolism may represent an important anti-inflammatory mechanism of GC action in the lung.     

Pulmonary intravascular macrophages metabolize arachidonic acid in vitro. Comparison with alveolar macrophages

Pulmonary intravascular macrophages are a recently identified component of the pulmonary mononuclear phagocyte system. It has been shown that alveolar macrophages are capable of metabolizing arachidonic acid (AA) to its biologically active inflammatory metabolites via the lipoxygenase and cyclooxygenase pathways. In this study, we have compared the ability of swine intravascular macrophages and alveolar macrophages to metabolize AA in vitro. Alveolar macrophages attached to a plastic substrate produced at least five identified AA metabolites including prostaglandin (PG)F2 alpha, hydroxyheptadecatrienoic acid (HHT), 5-hydroxyeicosatetraenoic acid (HETE), 12-HETE, and 15-HETE. In contrast, adherent intravascular macrophages produced eight identified metabolites including thromboxane (TX)B2, PGF2 alpha, PGD2, PGE2, HHT, 5-HETE, 12-HETE, and 15-HETE. The major lipoxygenase metabolite produced by both macrophage types was 5-HETE. The major cyclooxygenase metabolite produced by alveolar macrophages was PGF2 alpha, whereas the major metabolite produced by intravascular macrophages was HHT. Both macrophage populations treated with calcium ionophore (A23187) exhibited increased production of PGs, TXB2, leukotriene (LT)B4, 5-HETE, 12-HETE, and 15-HETE, but the most striking increase occurred in metabolism through the lipoxygenase pathway. The major lipoxygenase metabolite generated by ionophore-stimulated macrophages was 5-HETE, and in intravascular macrophages 12-HETE was also produced. Preincubation of macrophages with indomethacin and nordihydroguaiaretic acid attenuated the yield of cyclooxygenase metabolites and lipoxygenase metabolites, respectively. Studies of leukotriene formation demonstrated that both macrophage types produce LTC4 and LTB4 from the leukotriene precursor LTA4. Thus, we show that the pulmonary intravascular macrophage is capable of metabolizing AA and LTA4 to their inflammatory and vasoactive metabolites by the cyclooxygenase and lipoxygenase pathways.(ABSTRACT TRUNCATED AT 250 WORDS)     

Possible involvement of lipoxygenase pathway of arachidonic acid in rat pituitary hormone release in vitro

The roles of arachidonic acid (AA) and its lipoxygenase products in control of secretion of anterior pituitary hormones were studied in vitro using cultured cells. AA (10(-4)M) and 5-hydroxy-eicosatetraenoic acid (5HETE) (5 x 10(-6)M) significantly (p less than 0.05) stimulated the releases of LH, TSH, GH, PRL, ACTH and beta-endorphin (beta-E). Added leukotriene B4 (LTB4) (5 x 10(-6)M) also caused significant increases in the secretions of LH, GH, ACTH and beta-E. The other lipoxygenase metabolites tested, 12HETE, 15HETE, LTA4, LTC4 and LTD4, had no effect on the releases of anterior pituitary hormones. These results suggest that AA and 5-lipoxygenase metabolites may be involved in the control of the releases of anterior pituitary hormones.     

Production of arachidonic acid metabolites by macrophages exposed in vitro to asbestos, carbonyl iron particles, or calcium ionophore

Consequent to asbestos deposition, alveolar macrophages (AM) accumulate at alveolar duct bifurcations where they phagocytize fibers. Because phagocytosis can stimulate the release of arachidonic acid (AA) metabolites, the possibility that secretion of these powerful mediators of inflammation might be induced by chrysotile asbestos was investigated in vitro. Rat AM were treated in vitro with chrysotile asbestos, and the cyclooxygenase products--prostaglandins, thromboxane B2 (TXB2), 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT)--and lipoxygenase products--leukotrienes (LT), hydroxyeicosatetraenoic acids (HETE)--secreted in the medium were isolated by high-performance liquid chromatography. Composition of the AA metabolites released was compared with that from those stimulated by the calcium ionophore A 23187 (20 microM) and by another particulate phagocytic stimulus, i.e., carbonyl iron beads. Calcium ionophore stimulation induced a marked release of various AA metabolites in the medium from both the cyclooxygenase pathway (HHT, TXB2, and PGE2, in decreasing quantities, respectively) and the lipoxygenase pathway (LTB4, 5-HETE, 12-HETE, and LTC4). The major product was LTB4. Treatment of the macrophages with asbestos fibers induced the release of a similar array of AA metabolites, although there were smaller amounts of LTC4 and 12-HETE, but increased quantities of PGF2 alpha. A time course study showed a steady increase in metabolite production for 1 h, followed by a plateau. In addition, the amount of metabolites released was dependent on asbestos concentrations. Phagocytosis of iron beads induced the secretion of the same metabolites as asbestos stimulation, but in larger quantities, probably reflecting the lack of cytotoxicity of the particle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vasoactive systems in L-NAME hypertension: the role of inducible nitric oxide synthase

OBJECTIVES: The contribution of the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) to blood pressure (BP) maintenance was evaluated in rats with N(omega)-nitro-L-arginine methyl ester (L-NAME) hypertension. Furthermore, we studied the extent of nitric oxide (NO) synthesis inhibition and the participation of remaining NO in the counterbalance of pressor systems, with a special reference to inducible nitric oxide synthase (iNOS). METHODS: Wistar rats subjected to chronic L-NAME treatment (40 mg/kg per day for 4 weeks) were used. A consecutive blockade of RAS (captopril) and SNS (pentolinium) was followed by acute L-NAME injection. Dimethylguanidine or aminoguanidine were used to affect NO synthesis by iNOS. RESULTS: L-NAME hypertensive rats had borderline augmentation of depressor response to captopril injection, but their BP fall after pentolinium was considerably enhanced compared with controls. Residual BP (recorded after simultaneous blockade of the RAS and the SNS) was elevated by 20-40% in hypertensive rats. Pronounced inhibition of NO synthase activity (50% reduction in the aorta and myocardium) was detected in L-NAME hypertensive rats in which the BP rise elicited by acute L-NAME injection was considerably attenuated (by 60-80%). In contrast, acute administration of dimethylguanidine [mixed endothelial NO synthase (eNOS)/iNOS inhibitor] to hypertensive rats induced a major BP rise similar to that caused by L-NAME injection in controls. Aminoguanidine (a selective iNOS inhibitor) caused a substantial BP rise in L-NAME hypertensive rats only. CONCLUSION: The contribution of SNS to BP maintenance in L-NAME hypertension is more important than that of RAS. In L-NAME hypertensive rats the iNOS becomes a major source of hemodynamically important NO production, which is still insufficient to compensate prevailing vasoconstriction.