{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T01:39:27Z","timestamp":1768009167952,"version":"3.49.0"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2001,9]]},"abstract":"<jats:p>\n            The objective of this study was to test the hypothesis that renal interstitial (RI) cGMP is natriuretic in vivo. In conscious rats (n=8), urinary sodium excretion (U\n            <jats:sub>Na<\/jats:sub>\n            V) was significantly greater on days 3 and 4 of RI infusion of cGMP (1.17\u00b10.14 and 1.61\u00b10.11 mmol\/24 h, respectively) than during vehicle infusion (0.56\u00b10.15 and 0.70\u00b10.17 mmol\/24 h, respectively) (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.01). Similarly, U\n            <jats:sub>Na<\/jats:sub>\n            V was greater on days 3 and 4 of RI infusion of 8-bromo-cGMP (2.15\u00b10.42 and 2.16\u00b10.1 mmol\/24 h, respectively). Protein kinase G inhibitor Rp-8-pCPT-cGMPS reduced cGMP-induced and 8-bromo-cGMP-induced U\n            <jats:sub>Na<\/jats:sub>\n            V to control levels. Acute RI infusion of\n            <jats:sc>l<\/jats:sc>\n            -arginine (L-Arg, 40 mg \u00b7 kg\n            <jats:sup>\u22121<\/jats:sup>\n            \u00b7 min\n            <jats:sup>\u22121<\/jats:sup>\n            ), but not\n            <jats:sc>d<\/jats:sc>\n            -arginine, caused an increase in U\n            <jats:sub>Na<\/jats:sub>\n            V from 1.65\u00b10.11 to 4.07\u00b10.1 \u03bcmol\/30 min (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.01). This increase was blocked by RI infusion of\n            <jats:italic>N<\/jats:italic>\n            <jats:sup>G<\/jats:sup>\n            -nitro-\n            <jats:sc>l<\/jats:sc>\n            -arginine methyl ester (100 ng \u00b7 kg\n            <jats:sup>\u22121<\/jats:sup>\n            \u00b7 min\n            <jats:sup>\u22121<\/jats:sup>\n            ) by the phosphodiesterase (PDE II) activator 5,6DMcBIMP (0.01 \u03bcmol\/\u03bcL), by PDE II (0.03 U \u00b7 kg\n            <jats:sup>\u22121<\/jats:sup>\n            \u00b7 min\n            <jats:sup>\u22121<\/jats:sup>\n            ) itself, or by the soluble guanylyl cyclase inhibitor 1-\n            <jats:italic>H<\/jats:italic>\n            -[1,2,4]oxadiazolo-[4,2-\u03b1]quinoxalin-1-one (ODQ, 0.12 mg \u00b7 kg\n            <jats:sup>\u22121<\/jats:sup>\n            \u00b7 min\n            <jats:sup>\u22121<\/jats:sup>\n            ). The PDE II activator also blocked L-Arg-stimulated cGMP levels. The NO donor\n            <jats:italic>S<\/jats:italic>\n            -nitroso-\n            <jats:italic>N<\/jats:italic>\n            -acetylpenicillamine (SNAP, 0.12 \u03bcmol \u00b7 L\n            <jats:sup>\u22121<\/jats:sup>\n            \u00b7 kg\n            <jats:sup>\u22121<\/jats:sup>\n            \u00b7 min\n            <jats:sup>\u22121<\/jats:sup>\n            ) increased U\n            <jats:sub>Na<\/jats:sub>\n            V from 1.65\u00b10.11 to 2.93\u00b10.08 \u03bcmol\/30 min (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.01), and this response was blocked completely by ODQ. Renal arterial but not RI administration of the heat-stable enterotoxin of\n            <jats:italic>Escherichia coli<\/jats:italic>\n            induced natriuresis. RA infusion of cGMP (3 \u03bcg\/min) increased U\n            <jats:sub>Na<\/jats:sub>\n            V, renal blood flow (RBF), and glomerular filtration rate (GFR). Renal cortical interstitial cGMP infusion increased U\n            <jats:sub>Na<\/jats:sub>\n            V with no effect on total RBF, renal cortical blood flow, or GFR. Similarly, the natriuretic actions of renal interstitial L-Arg or SNAP were not accompanied by any change in RBF or GFR. Medullary cGMP infusion had no effect on U\n            <jats:sub>Na<\/jats:sub>\n            V, total RBF, or medullary blood flow. Texas red-labeled cGMP infused via the RI space was distributed exclusively to cortical renal tubular cells. The results demonstrate that RI cGMP inhibits renal tubular sodium absorption via protein kinase G independently of hemodynamic changes. These observations indicate that the cortical interstitial compartment provides a potentially important domain for cell-to-cell signaling within the kidney.\n          <\/jats:p>","DOI":"10.1161\/01.hyp.38.3.309","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:25:31Z","timestamp":1339460731000},"page":"309-316","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":48,"title":["Renal Interstitial cGMP Mediates Natriuresis by Direct Tubule Mechanism"],"prefix":"10.1161","volume":"38","author":[{"given":"Xiao-Hong","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Virginia, School of Medicine, Charlottesville."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helmy M.","family":"Siragy","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Virginia, School of Medicine, Charlottesville."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert M.","family":"Carey","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Virginia, School of Medicine, Charlottesville."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_1_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1054-3589(08)60047-2"},{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)63473-8"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2744(69)90362-3"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90497-3"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2000.278.2.F180"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.19.6.780"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115709"},{"key":"e_1_3_1_8_2","first-page":"F344","volume":"264","year":"1993","unstructured":"Lahera V, Navarro J, Biondi ML, Ruilope LM, Romero JC. 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