Chronic nitroglycerine administration reduces endothelial nitric oxide production in rabbit mesenteric resistance artery
Chronic nitroglycerine administration reduces endothelial nitric oxide production in rabbit mesenteric resistance artery
复制标题
DOI：
10.1038/sj.bjp.0706365
复制
发表时间：
2005-10
影响因子：
7.3
通讯作者：
Tamao Yamamoto;J. Kajikuri;Yoshimasa Watanabe;Yoshikatsu Suzuki;K. Suzumori;T. Itoh
中科院分区：
文献类型：
--
作者：
Tamao Yamamoto;J. Kajikuri;Yoshimasa Watanabe;Yoshikatsu Suzuki;K. Suzumori;T. Itoh
我们研究了硝酸甘油(NTG)10天的活体处理是否会抑制阻力动脉内皮细胞产生一氧化氮，如果是的话，可能的机制是什么。ACh增加了兔肠系膜阻力动脉内皮细胞内一氧化氮浓度([NO]i；用一氧化氮敏感的荧光染料二氨基荧光素-2估计)。在NTG处理的兔的动脉中，这种影响明显小于对照组的动脉。血管紧张素Ⅱ受体(AT1Rs)阻断剂奥美沙坦与NTG合用，以及超氧化物清除剂锰(III)四(4-苯甲酸)卟啉(Mn-TBAP)、蛋白激酶C(PKC)抑制剂GF109203X或1-精氨酸(加或不加叶酸活性形式(5-甲基四氢叶酸))与NTG处理的动脉共同孵育，可防止NTG处理的兔血管内皮细胞[NO]i减少。NTG处理的兔动脉内皮细胞超氧化物的产生(用乙锭荧光法估计)显著增加。在体内给予奥美沙坦和NTG，以及在体外应用Mn-tBAP或GF109203X(但不包括5-甲基四氢叶酸+L-精氨酸)。ACH增加内皮细胞内钙浓度(用钙敏感染料Fura 2估计)，这种增加在NTG处理的兔和对照组之间没有显著差异。我们得出结论，NTG处理的兔肠系膜阻力动脉内皮一氧化氮的产生减少，可能是通过超氧化物介导的L-精氨酸的生物利用度降低所致。AT1R-PKC通路的激活可能参与增加超氧化物的产生。英国药理学杂志(2005)146,534-542。DOI：10.1038/sj.bjp.0706365
We investigated whether 10 days'in vivotreatment with nitroglycerine (NTG) would inhibit nitric oxide production by the endothelial cells of resistance arteriesex vivoand, if so, what the underlying mechanism might be.ACh increased the intracellular nitric oxide concentration ([NO]i; estimated using the nitric oxide‐sensitive fluorescent dye diaminofluorescein‐2) within the endothelial cells of rabbit mesenteric resistance arteries. This effect was significantly smaller in arteries isolated from NTG‐treated rabbits than in those from control rabbits. The reduction in endothelial [NO]iin NTG‐treated rabbits was prevented when olmesartan (blocker of type 1 angiotensin II receptors (AT1Rs)) was coadministeredin vivowith NTG and also when the superoxide scavenger manganese (III) tetrakis‐(4‐benzoic acid) porphyrin (Mn‐TBAP), the protein kinase C (PKC) inhibitor GF109203X orL‐arginine (with or without the active form of folate (5‐methyltetrahydrofolate)) was incubated with the arteriesin vitro.Endothelial cell superoxide production (estimated by ethidium fluorescence) was greatly increased in arteries from NTG‐treated rabbits. This was normalized byin vivocoadministration of olmesartan with NTG and also byin vitroapplication of Mn‐TBAP or GF109203X (but not of 5‐methyltetrahydrofolate+L‐arginine).ACh increased the intracellular Ca2+concentration (estimated using the Ca2+‐sensitive dye Fura 2) within endothelial cells, the increase being not significantly different between NTG‐treated rabbits and control rabbits.We conclude that in NTG‐treated rabbits, endothelial nitric oxide production in mesenteric resistance arteries is reduced, possibly through a reduction in the bioavailability ofL‐arginineviaan action mediated by superoxide. Activation of the AT1R–PKC pathway may be involved in increasing superoxide production.British Journal of Pharmacology(2005)146, 534–542. doi:10.1038/sj.bjp.0706365