{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T01:16:30Z","timestamp":1712193390269},"reference-count":44,"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":[[2004,6]]},"abstract":"<jats:p>We examined whether amiloride, an agent that possesses epithelial sodium channel (ENaC)- and sodium\/hydrogen exchange (NHE)-inhibitory activities, would exhibit renal vascular protection in saline-drinking, stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP received amiloride (1.0 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>, n = 6) or deionized water (3 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>, n = 6) for 5 wk starting at 61 days of age. Systolic blood pressure (SBP) did not differ among the groups, and there was no difference in the average daily urine output, sodium excretion, or potassium excretion. Terminal urinary protein excretion, blood urea nitrogen, and renal thrombotic microangiopathic lesions were markedly reduced in the amiloride group with no difference in plasma renin activity (PRA). In a survival protocol, SHRSP infused subcutaneously with benzamil (0.7 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>, n = 8), a selective ENaC inhibitor, dimethylamiloride (0.7 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>, n = 8), a selective NHE inhibitor, or vehicle ( n = 7) had comparable SBP. Dimethylamiloride nonetheless prolonged survival of SHRSP ( P &lt; 0.005 vs. vehicle), and benzamil-treated SHRSP lived even longer ( P &lt; 0.0001 vs. vehicle; P &lt; 0.05 vs. dimethylamiloride). In a separate series, plasma potassium concentration was elevated by dimethylamiloride (3.4 \u00b1 0.1 meq\/l, n = 8) and benzamil (3.3 \u00b1 0.1 meq\/l, n = 8) relative to vehicle (3.0 \u00b1 0.1 meq\/l, n = 8) at 4 but not at 24 h after dosing. These findings suggest the involvement of a sodium transport mechanism in the development of thrombotic microangiopathy in SHRSP, unrelated to marked changes in arterial pressure, PRA, plasma potassium, or urinary water and electrolyte excretion.<\/jats:p>","DOI":"10.1152\/ajprenal.00355.2003","type":"journal-article","created":{"date-parts":[[2004,3,2]],"date-time":"2004-03-02T01:46:56Z","timestamp":1078192016000},"page":"F1185-F1192","source":"Crossref","is-referenced-by-count":8,"title":["Sodium transport antagonism reduces thrombotic microangiopathy in stroke-prone spontaneously hypertensive rats"],"prefix":"10.1152","volume":"286","author":[{"given":"Reza","family":"Sepehrdad","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Praveen N.","family":"Chander","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gagan","family":"Singh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr","given":"Charles T.","family":"Stier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.35.5.1099"},{"key":"R2","unstructured":"Benos DJ.Amiloride: a molecular probe of sodium transport in tissues and cells.Am J Physiol Cell Physiol242: C131\u2013C145, 1982."},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.73.3.307"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.00631.x"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1210\/endo.142.4.8095"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199301000-00006"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1038\/367463a0"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M311783200"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000078960.15147.05"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.5.2514"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.25.1.117"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1527-3466.1999.tb00009.x"},{"key":"R13","unstructured":"Drummond HA, Gebremedhin D, and Harder DR.DEG\/ENaC proteins: components of a vascular mechanosensor (Abstract).Hypertension42: 390, 2003."},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1997.77.2.359"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.4275"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1994.267.5.E754"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1995.269.3.H1044"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.34.21075"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1159\/000138970"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1007\/BF01871102"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1016\/0039-128X(94)00016-6"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7840"},{"key":"R23","doi-asserted-by":"crossref","unstructured":"Nagaoka A, Iwatsuka H, Suzuoki Z, and Okamoto K.Genetic predisposition to stroke in spontaneously hypertensive rats.Am J Physiol230: 1354\u20131359, 1976.","DOI":"10.1152\/ajplegacy.1976.230.5.1354"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1159\/000188679"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.24.16973"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00015.2002"},{"key":"R27","unstructured":"Okamoto K, Yamori Y, and Nagaoka A.Establishment of the stroke-prone spontaneously hypertensive rat (SHR).Circ Res34: I-143\u2013I-153, 1974."},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-2760(01)00439-8"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1161\/hy1101.095010"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.31.1.451"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-2760(01)00432-5"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(96)90155-9"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1992.37"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-7061(03)00006-2"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1210\/edrv.23.2.0458"},{"key":"R36","unstructured":"Stier CT Jr, Adler LA, Levine S, and Chander PN.Stroke prevention by losartan in stroke-prone spontaneously hypertensive rats.J Hypertens11,Suppl3: S37\u2013S42, 1993."},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.13.2.115"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/4.8.680"},{"key":"R39","unstructured":"Stier CT Jr, Mahboubi K, DiPippo VA, Levine S, and Chander PN.The antiproteinuric action of enalapril in stroke-prone spontaneously hypertensive rats is unrelated to alterations in urinary prostaglandins.J Pharmacol Exp Ther260: 1410\u20131415, 1992."},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215709"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1997.272.3.C901"},{"key":"R42","doi-asserted-by":"crossref","unstructured":"Vigne P, Champigny G, Marsault R, Barbry P, Frelin C, and Lazdunski M.A new type of amiloride-sensitive cationic channel in endothelial cells of brain microvessels.J Biol Chem264: 7663\u20137668, 1989.","DOI":"10.1016\/S0021-9258(18)83285-9"},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1016\/0039-128X(94)00027-A"},{"key":"R44","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.6.1.49"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00355.2003","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T23:32:13Z","timestamp":1623713533000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00355.2003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,6]]},"references-count":44,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2004,6]]}},"alternative-id":["10.1152\/ajprenal.00355.2003"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00355.2003","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,6]]}}}