{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T21:29:24Z","timestamp":1778275764202,"version":"3.51.4"},"reference-count":35,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2005,12]]},"abstract":"<jats:p>Acute administration of loop diuretics like furosemide leads to a stimulation of renin secretion, an effect thought to result from inhibition of Na-K-2Cl cotransporter (NKCC2)-mediated salt transport at the luminal surface of the macula densa (MD). However, loop diuretics also inhibit NKCC1, the second isoform of the Na-K-2Cl cotransporter, with similar potency. In the present study, we examined the influence of furosemide on renin secretion in NKCC1-deficient mice to distinguish between effects of the loop diuretic involving NKCC2 and, by implication, the MD pathway, and effects that might occur via inhibition of NKCC1. Baseline plasma renin concentration (PRC) was 1,212 \u00b1 211 in NKCC1+\/+ ( n = 13) and 3,851 \u00b1 579 ng ANG I\u00b7ml<jats:sup>\u22121<\/jats:sup>\u00b7h<jats:sup>\u22121<\/jats:sup>in NKCC1\u2212\/\u2212 mice ( n = 14; P = 0.00024). Acute administration of furosemide (50 mg\/kg i.p.) increased PRC significantly to 9,324 \u00b1 1,018 ng ANG I\u00b7ml<jats:sup>\u22121<\/jats:sup>\u00b7h<jats:sup>\u22121<\/jats:sup>in NKCC1+\/+ ( n = 13; P &lt; 0.0001 compared with basal) and to 14,188 \u00b1 2,274 ng ANG I\u00b7ml<jats:sup>\u22121<\/jats:sup>\u00b7h<jats:sup>\u22121<\/jats:sup>in NKCC1\u2212\/\u2212 mice [ n = 14; P = 0.0002 compared with basal; P = 0.034 compared with wild-type (WT) plus furosemide]. Renin mRNA expression was about threefold higher in NKCC1\u2212\/\u2212 compared with WT mice. There was considerable recruitment of granular cells to upstream regions of afferent arterioles in NKCC1\u2212\/\u2212 mice. Patch-clamp studies in single juxtaglomerular granular (JG) cells from WT mice showed an \u223c10% increase in membrane capacitance during incubation with furosemide (10<jats:sup>\u22124<\/jats:sup>M), indicating a direct effect of the loop diuretic on renin secretion. No effect of furosemide on membrane capacitance was observed in JG cells from NKCC1-deficient mice. Furosemide (10<jats:sup>\u22123<\/jats:sup>M) significantly stimulated renin release from primary cultures of JG cells from WT mice, whereas no response was observed in NKCC1\u2212\/\u2212 mice. Our data suggest that a functional NKCC1 suppresses basal renin release, at least in part, through a direct effect on JG cells.<\/jats:p>","DOI":"10.1152\/ajprenal.00455.2004","type":"journal-article","created":{"date-parts":[[2005,8,17]],"date-time":"2005-08-17T02:39:04Z","timestamp":1124246344000},"page":"F1185-F1192","source":"Crossref","is-referenced-by-count":66,"title":["Contribution of the basolateral isoform of the Na-K-2Cl<sup>\u2212<\/sup>cotransporter (NKCC1\/BSC2) to renin secretion"],"prefix":"10.1152","volume":"289","author":[{"given":"Hayo","family":"Castrop","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John N.","family":"Lorenz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pernille B.","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulla","family":"Friis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane","family":"Mizel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mona","family":"Oppermann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boye L.","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josie","family":"Briggs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ole","family":"Sk\u00f8tt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jurgen","family":"Schnermann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1993.265.1.F151"},{"key":"R2","doi-asserted-by":"crossref","unstructured":"Castrop H, Schweda F, Mizel D, Huang Y, Briggs J, Kurtz A, and Schnermann J.Permissive role of nitric oxide in macula densa control of renin secretion.Am J Physiol Renal Physiol286: F848\u2013F857, 2004.","DOI":"10.1152\/ajprenal.00272.2003"},{"key":"R3","doi-asserted-by":"crossref","unstructured":"Chomczynski Pand Sacchi N.Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.Anal Biochem162: 156\u2013159, 1987.","DOI":"10.1016\/0003-2697(87)90021-2"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.37.4.464"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1038\/9713"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.38.26946"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.84.8.929"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000017622.25365.71"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-201X.2004.01310.x"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000085041.70276.3D"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.62.1.515"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1990.70.4.1067"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-001-0521-y"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00522.2002"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.26.1.137"},{"key":"R16","doi-asserted-by":"crossref","unstructured":"Ikebe M, Nonoguchi H, Nakayama Y, Tashima Y, and Tomita K.Upregulation of the secretory-type Na+\/K+\/2Cl\u2212cotransporter in the kidney by metabolic acidosis and dehydration in rats.J Am Soc Nephrol12: 423\u2013430, 2001.","DOI":"10.1681\/ASN.V123423"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.7.3_Pt_2.I49"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1996.271.3.F659"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.58.030196.003245"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118844"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1990.258.5.F1466"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1991.260.4.F486"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00083.2002"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.21.6712"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1998.275.6.F885"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118834"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114373"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8553"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1007\/BF00584628"},{"key":"R30","unstructured":"Schnermann Jand Briggs JP.Function of the juxtaglomerular apparatus: control of glomerular hemodynamics and renin secretion. 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