{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T10:52:09Z","timestamp":1791111129231,"version":"4.1.0"},"reference-count":28,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2001,8,1]]},"abstract":"<jats:p>Vasoconstrictors activate the Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>cotransporter NKCC1 in rat aortic smooth muscle, but the mechanism is unknown. Efflux of<jats:sup>86<\/jats:sup>Rb<jats:sup>+<\/jats:sup>from rat aorta in response to phenylephrine (PE) was measured in the absence and presence of bumetanide, a specific inhibitor of NKCC1. Removal of extracellular Ca<jats:sup>2+<\/jats:sup>completely abolished the activation of NKCC1 by PE. This was not due to inhibition of Ca<jats:sup>2+<\/jats:sup>-dependent K<jats:sup>+<\/jats:sup>channels since blocking these channels with Ba<jats:sup>2+<\/jats:sup>in Ca<jats:sup>2+<\/jats:sup>-replete solution did not prevent activation of NKCC1 by PE. Stimulation of NKCC1 by PE was inhibited 70% by 75 \u03bcM ML-9, 97% by 2 \u03bcM wortmannin, and 70% by 2 mM 2,3-butanedione monoxime, each of which inhibited isometric force generation in aortic rings. Bumetanide-insensitive Rb<jats:sup>+<\/jats:sup>efflux, an indication of Ca<jats:sup>2+<\/jats:sup>-dependent K<jats:sup>+<\/jats:sup>channel activity, was reduced by ML-9 but not by the other inhibitors. Stretching of aortic rings on tubing to increase lumen diameter to 120% of normal almost completely blocked the stimulation of NKCC1 by PE without inhibiting the stimulation by hypertonic shrinkage. We conclude that activation of the Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>cotransporter by PE is the direct result of smooth muscle contraction through Ca<jats:sup>2+<\/jats:sup>-dependent activation of myosin light chain kinase. This indicates that the Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>cotransporter is regulated by the contractile state of vascular smooth muscle.<\/jats:p>","DOI":"10.1152\/ajpcell.2001.281.2.c579","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T20:41:57Z","timestamp":1514148117000},"page":"C579-C584","source":"Crossref","is-referenced-by-count":66,"title":["Contractile regulation of the Na<sup>+<\/sup>-K<sup>+<\/sup>-2Cl<sup>\u2212<\/sup>cotransporter in vascular smooth muscle"],"prefix":"10.1152","volume":"281","author":[{"given":"Fatma","family":"Akar","sequence":"first","affiliation":[{"name":"Renal Division, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gengru","family":"Jiang","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Paul","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Molecular Physiology, University of Cincinnati, Cincinnati, Ohio 45267"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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