{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T04:11:13Z","timestamp":1745554273598,"version":"3.40.4"},"reference-count":2,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[1999,1,1]],"date-time":"1999-01-01T00:00:00Z","timestamp":915148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[1999,1,1]],"date-time":"1999-01-01T00:00:00Z","timestamp":915148800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Kidney Blood Press Res"],"published-print":{"date-parts":[[1999]]},"abstract":"<b>Background:<\/b> Recombinant human erythropoietin (rHuEpo) is the treatment of choice in anemia associated with end\u2013stage renal disease. Its major side effect is hypertension, which occurs in 8\u201330% of uremic patients. The exact mechanism of rHuEpo\u2013induced hypertension has not been fully elucidated, and several possibilities have been proposed, such as a direct vascular effect of the drug with a shift in the balance of constrictor and relaxing endothelial factors (endothelins and nitric oxide (NO)). Recent papers suggested an enhanced rather than reduced activity of endogenous NO system in rats with normal renal function and rHuEpo\u2013induced hypertension. Our study was designed to verify whether, in spite of enhanced activity of the renal NO system, rHuEpo may affect endothelium\u2013dependent (acetylcholine\u2013induced) and\/or endothelium\u2013independent (sodium nitroprusside\u2013induced) vasorelaxation and to evaluate basal NO release by the infusion of N<sup>G<\/sup>\u2013nitro\u2013L\u2013arginine methyl ester (L\u2013NAME) in an isolated and perfused rat kidney model. <b>Methods: <\/b>To investigate this hypothesis, we have determined systemic and renal NO activity in Wistar rats treated with a hypertensive dose of rHuEpo (150 IU\/kg b.w. every other day for 2 weeks) by measuring stable NO metabolites (NO<sub>2<\/sub>+NO<sub>3<\/sub>) in the urine and have also evaluated variations in renal vascular resistance after the injection of Ach, SNP and the infusion of L\u2013NAME. <b>Results: <\/b>Hematocrit, hemoglobin concentration and arterial blood pressure were significantly increased in the treated group as compared with the controls. Urinary excretion of NO<sub>2<\/sub>+NO<sub>3<\/sub> was significantly higher in treated than in the controls (438\u00b166 vs. 294\u00b136 nM\/ml\/min, p<0.01, respectively). There were no significant differences in the dose\u2013response curves to Ach and SNP between the two groups. The renal vasoconstriction following the infusion of L\u2013NAME was also similar in the two groups. <b>Conclusions: <\/b>The analysis of our results seems to indicate that the endogenous NO system activity was enhanced in rHuEpo\u2013induced hypertension in rats with normal renal function and a resistance to NO was not developed in renal circulation. Further studies seem to be necessary to better clarify the exact mechanisms underlying the development of rHuEpo\u2013induced hypertension.<\/jats:p>","DOI":"10.1159\/000025920","type":"journal-article","created":{"date-parts":[[2003,4,15]],"date-time":"2003-04-15T09:24:25Z","timestamp":1050398665000},"page":"140-145","source":"Crossref","is-referenced-by-count":12,"title":["Nitric Oxide\u2013Dependent Renal Vasodilatation Is Not Altered in Rat with rHuEpo\u2013Induced Hypertension"],"prefix":"10.1159","volume":"22","author":[{"given":"M.","family":"Migliori","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Taccola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"Panichi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"De Pietro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Andreini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Di Benedetto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Filippi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Palla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Giovannini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[1999,6,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(93)90066-C"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1038\/377239a0"}],"container-title":["Kidney and Blood Pressure Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/25920","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/25920","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T03:52:36Z","timestamp":1745466756000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000025920"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999]]},"references-count":2,"journal-issue":{"issue":"3","published-online":{"date-parts":[[1999,7,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000025920","archive":["Portico"],"relation":{},"ISSN":["1420-4096","1423-0143"],"issn-type":[{"type":"print","value":"1420-4096"},{"type":"electronic","value":"1423-0143"}],"subject":[],"published":{"date-parts":[[1999]]}}}