Vascular smooth muscle cell membrane depolarization after NOS inhibition hypertension.
Vascular smooth muscle cell membrane depolarization after NOS inhibition hypertension.
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NOS抑制高血压后血管平滑肌细胞膜去极化。
DOI：
10.1152/ajpheart.00824.2001
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Kanagy,NancyL
中科院分区：
文献类型：
--
作者：
Bratz,IanN;Falcon,Ricardo;Partridge,LDonald;Kanagy,NancyL
Nitric oxide (NO) synthase (NOS) inhibition withNω-nitro-l-arginine (l-NNA) producesl-NNA hypertensive rats (LHR), which exhibit increased sensitivity to voltage-dependent Ca2+channel-mediated vasoconstriction. We hypothesized that enhanced contractile responsiveness after NOS inhibition is mediated by depolarization of membrane potential (Em) through attenuated K+channel conductance.Emmeasurements demonstrated that LHR vascular smooth muscle cells (VSMCs) are depolarized in open, nonpressurized (−44.5 ± 1.0 mV in control vs. −36.8 ± 0.8 mV in LHR) and pressurized mesenteric artery segments (−41.8 ± 1.0 mV in control vs. −32.6 ± 1.4 mV in LHR). Endothelium removal or exogenousl-NNA depolarized control VSMCs but not LHR VSMCs. Superfusedl-arginine hyperpolarized VSMCs from both the control and LHR groups and reversedl-NNA-induced depolarization (−44.5 ± 1.0 vs. −45.8 ± 2.1 mV). A Ca2+-activated K+channel agonist, NS-1619 (10 μM), hyperpolarized both groups of arteries to a similar extent (from −50.8 ± 1.0 to −62.5 ± 1.2 mV in control and from −43.7 ± 1.1 to −55.6 ± 1.2 mV in LHR), althoughEmwas still different in the presence of NS-1619. In addition, superfused iberiotoxin (50 nM) depolarized both groups similarly. Increasing the extracellular K+concentration from 1.2 to 45 mM depolarizedEm, as predicted by the Goldman-Hodgkin-Katz equation. These data support the hypothesis that loss of NO activation of K+channels contributes to VSMC depolarization inl-NNA-induced hypertension without a change in the number of functional large conductance Ca2+-activated K+channels.
