Flavin adenine dinucleotide may release preformed stores of nitrosyl factors from the vascular endothelium of conscious rats
Flavin adenine dinucleotide may release preformed stores of nitrosyl factors from the vascular endothelium of conscious rats
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DOI：
10.1097/fjc.0b013e31805c1646
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发表时间：
2007-08-01
影响因子：
3
通讯作者：
Lewis, Stephen J.
中科院分区：
文献类型：
--
作者：
Hashmi-Hill, Maleka P.;Sandock, Kevin;Lewis, Stephen J.
本研究确定黄素腺嘌呤二核苷酸（FAD）是否可通过释放预先形成的内皮衍生亚硝基因子引起意识大鼠血管舒张。注射1-6（注射1-6）FAD （2.5 μ mol/kg， IV）在盐水处理大鼠中引起明显的血管扩张反应。注射(1)FAD可引起L-NAME处理大鼠明显的血管扩张，这些大鼠使用一氧化氮（NO）合成抑制剂n - g -硝基- l -精氨酸（L-NAME; 50 μ mol/kg， IV）进行预处理，而注射（2-6）引起的反应逐渐减弱，因此注射(6)引起的反应较小。由内皮依赖性激动剂乙酰胆碱引起的血管扩张反应在注射1-6次FAD的l - name处理大鼠中明显减弱，而在注射1-6次FAD的盐水处理大鼠中则没有减弱。注射FAD后，l - s -亚硝基半胱氨酸和NO供体硝普钠的血管舒张作用均未减弱。结合研究表明，与生理盐水+生理盐水（1-6）或生理盐水+生理盐水（1-6）或生理盐水+生理盐水1-6处理的大鼠相比，L-NAME +生理盐水注射（1-6）或生理盐水+生理盐水注射（1-6）处理的大鼠胸主动脉内皮中毒毒碱M-3受体的密度增加。l - name处理的大鼠对注射FAD的反应逐渐丧失，加上对乙酰胆碱的反应丧失，表明FAD引起内皮细胞中亚硝基因子囊泡池的使用依赖性耗竭，而在没有NO合成的情况下，这些亚硝基因子无法得到补充。
This study determined whether flavin adenine dinucleotide (FAD) may elicit vasodilation in conscious rats via release of preformed endothelium-derived nitrosyl factors. Injections 1-6 (inj 1-6) of FAD (2.5 mu mol/kg, IV) elicited pronounced and equivalent vasodilator responses in saline-treated rats. Inj(1) of FAD elicited pronounced vasodilation in L-NAME-treated rats pretreated with the nitric oxide (NO) synthesis inhibitor, N-G-nitro-L-arginine (L-NAME; 50 mu mol/kg, IV), whereas Inj(2-6) elicited progressively smaller responses such that inj(6) elicited minor responses. The vasodilator responses elicited by the endothelium-dependent agonist, acetylcholine, were markedly attenuated in L-NAME-treated rats that had received inj(1-6) of FAD but not in saline-treated rats that had received inj1-6 of FAD. The vasodilator actions of L-S-nitrosocysteine and the NO donor, sodium nitroprusside, were not diminished after the injections of FAD in saline- or in L-NAME-treated rats. Binding studies demonstrated that the densities of muscarinic M-3 receptors were increased in thoracic aorta endothelium of rats treated with L-NAME + inj(1-6) of saline or LNAME + inj(1-6) of FAD as compared to rats treated with saline + inj(1-6) of saline or saline + inj 1-6 of FAD. The progressive loss of response to injections of FAD in L-NAME-treated rats coupled with the loss of response to acetylcholine suggests that FAD elicits the use-dependent depletion of vesicular pools of nitrosyl factors in endothelial cells that cannot be replenished in the absence of NO synthesis.