{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T13:15:28Z","timestamp":1772889328595,"version":"3.50.1"},"reference-count":42,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2002,5,1]]},"abstract":"<jats:p>Nitric oxide (NO) synthase (NOS) inhibition with N<jats:sup>\u03c9<\/jats:sup>-nitro-l-arginine (l-NNA) produces l-NNA hypertensive rats (LHR), which exhibit increased sensitivity to voltage-dependent Ca<jats:sup>2+<\/jats:sup>channel-mediated vasoconstriction. We hypothesized that enhanced contractile responsiveness after NOS inhibition is mediated by depolarization of membrane potential ( E<jats:sub>m<\/jats:sub>) through attenuated K<jats:sup>+<\/jats:sup>channel conductance. E<jats:sub>m<\/jats:sub>measurements demonstrated that LHR vascular smooth muscle cells (VSMCs) are depolarized in open, nonpressurized (\u221244.5 \u00b1 1.0 mV in control vs. \u221236.8 \u00b1 0.8 mV in LHR) and pressurized mesenteric artery segments (\u221241.8 \u00b1 1.0 mV in control vs. \u221232.6 \u00b1 1.4 mV in LHR). Endothelium removal or exogenous l-NNA depolarized control VSMCs but not LHR VSMCs. Superfused l-arginine hyperpolarized VSMCs from both the control and LHR groups and reversedl-NNA-induced depolarization (\u221244.5 \u00b1 1.0 vs. \u221245.8 \u00b1 2.1 mV). A Ca<jats:sup>2+<\/jats:sup>-activated K<jats:sup>+<\/jats:sup>channel agonist, NS-1619 (10 \u03bcM), hyperpolarized both groups of arteries to a similar extent (from \u221250.8 \u00b1 1.0 to \u221262.5 \u00b1 1.2 mV in control and from \u221243.7 \u00b1 1.1 to \u221255.6 \u00b1 1.2 mV in LHR), although E<jats:sub>m<\/jats:sub>was still different in the presence of NS-1619. In addition, superfused iberiotoxin (50 nM) depolarized both groups similarly. Increasing the extracellular K<jats:sup>+<\/jats:sup>concentration from 1.2 to 45 mM depolarized E<jats:sub>m<\/jats:sub>, as predicted by the Goldman-Hodgkin-Katz equation. These data support the hypothesis that loss of NO activation of K<jats:sup>+<\/jats:sup>channels contributes to VSMC depolarization inl-NNA-induced hypertension without a change in the number of functional large conductance Ca<jats:sup>2+<\/jats:sup>-activated K<jats:sup>+<\/jats:sup>channels.<\/jats:p>","DOI":"10.1152\/ajpheart.00824.2001","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T20:02:41Z","timestamp":1425412961000},"page":"H1648-H1655","source":"Crossref","is-referenced-by-count":19,"title":["Vascular smooth muscle cell membrane depolarization after NOS inhibition hypertension"],"prefix":"10.1152","volume":"282","author":[{"given":"Ian N.","family":"Bratz","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Physiology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo","family":"Falcon","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L. 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