Use-dependent loss of acetylcholine- and bradykinin-mediated vasodilation after nitric oxide synthase inhibition - Evidence for preformed stores of nitric oxide-containing factors in vascular endothelial cells
Use-dependent loss of acetylcholine- and bradykinin-mediated vasodilation after nitric oxide synthase inhibition - Evidence for preformed stores of nitric oxide-containing factors in vascular endothelial cells
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DOI：
10.1161/01.hyp.28.3.354
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发表时间：
1996-09-01
期刊：
影响因子：
8.3
通讯作者：
Lewis, SJ
中科院分区：
文献类型：
--
作者：
Davisson, RL;Bates, JN;Lewis, SJ
在本研究中，我们研究了内皮依赖性血管扩张剂乙酰胆碱和缓动素释放含一氧化氮因子的可能性，连续注射选择剂量的乙酰胆碱（1.18+/-0.3 μ g/kg IV）或缓动素（5 μ g/kg IV）在清醒大鼠的交感神经完整和交感神经去神经后肢中引起可重复性的降压和血管扩张剂反应。在给予一氧化氮合成抑制剂n -omega-硝基- l -精氨酸甲酯（L-NAME, 25 μ mol/kg IV）后，第一次注射乙酰胆碱或缓激肽产生明显的抑制和血管扩张反应，缓激肽的情况下，比L-NAME给药前观察到的更大。然而，每次连续注射乙酰胆碱和缓激肽产生的反应逐渐减弱，因此，后来的注射引起低血压和血管舒张明显减轻。这种内皮依赖性血管舒张的“使用依赖性”丧失不是由于含一氧化氮因子的血管舒张作用减弱，因为一氧化氮供体硝普钠（32 μ g/kg IV）和s -亚硝基硫醇化合物5-亚硝基半胱氨酸（200 nmol/kg IV）的血管舒张作用在L-NAME存在下增强。这些结果表明，乙酰胆碱和缓激肽在l - name治疗的大鼠血液动力学作用的使用依赖性丧失可能是由于一种因子的释放和随后的消耗，该因子的合成取决于一氧化氮的生物利用度。综上所述，这些结果表明，在抵抗血管的内皮中存在预先形成的含一氧化氮因子池，内皮依赖性激动剂至少在一定程度上通过动员这些预先形成的池来发挥血管松弛作用。
In the present study, we examined the possibility that the endothelium-dependent vasodilators acetylcholine and bradykinin release preformed poets of nitric oxide-containing factors, Successive injections of selected doses of acetylcholine (1.18+/-0.3 mu g/kg IV) or bradykinin (5 mu g/kg IV) caused reproducible hypotensive and vasodilator responses within sympathetically intact and sympathetically denervated hindlimbs of conscious rats. After administration of the nitric oxide synthesis inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME, 25 mu mol/kg IV), time first injection of acetylcholine or bradykinin produced pronounced depressor and vasodilator responses that, in the case of bradykinin, were greater than those observed before L-NAME administration. However, each successive injection of acetylcholine and bradykinin produced progressively smaller responses, such that the later injections elicited a markedly diminished hypotension and vasodilation. This ''use-dependent'' loss of endothelium-dependent vasodilation was not due to the diminished vasorelaxant potency of nitric oxide-containing factors because the vasodilator effects of the nitric oxide donor sodium nitroprusside (32 mu g/kg IV) and the S-nitrosothiol compound 5-nitrosocysteine (200 nmol/kg IV) were augmented in the presence of L-NAME. These results suggest that the use-dependent loss of the hemodynamic effects of acetylcholine and bradykinin in L-NAME-treated rats may be due to the release and subsequent depletion of a factor whose synthesis depends on the bioavailability of nitric oxide. Taken together, these results suggest that preformed pools of nitric oxide-containing factors exist within the endothelium of resistance vessels and that endothelium-dependent agonists exert their vasorelaxant effects at least in part by the mobilization of these preformed pools.