{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,15]],"date-time":"2025-06-15T04:40:07Z","timestamp":1749962407567,"version":"3.41.0"},"reference-count":50,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2017,5,1]]},"abstract":"<jats:p>Our aim was to investigate whether blockade of calcium channels (CCs) or angiotensin II type 1 receptors (AT1R) modulates renal responses to nitric oxide synthesis inhibition (NOSI) in humans. Fourteen sodium-replete, healthy volunteers underwent 90-min infusions of 3.0 \u03bcg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7min<jats:sup>\u22121<\/jats:sup>N<jats:sup>G<\/jats:sup>-nitro-l-arginine methyl ester (l-NAME) on 3 occasions, preceded by 3 days of either placebo (PL), 10 mg of manidipine (MANI), or 50 mg of losartan (LOS). At each phase, mean arterial pressure (MAP), glomerular filtration rate (GFR; inulin), renal blood flow (RBF; p-aminohippurate), urinary sodium (UNaV), and 8-isoprostane (U8-iso-PGF2\u03b1V; an oxidative stress marker) were measured. With PL + l -NAME, the following changes were observed: +6% MAP ( P &lt; 0.005 vs. baseline), \u221210% GFR, \u221220% RBF, \u221249% UNaV ( P &lt; 0.001), and +120% U8-iso-PGF2\u03b1V ( P &lt; 0.01). In contrast, MAP did not increase during LOS + l-NAME or MANI + l-NAME ( P &gt; 0.05 vs. baseline), whereas renal changes were the same during LOS + l-NAME vs. PL + l-NAME (ANOVA, P &gt; 0.05). However, during MANI + l-NAME, changes vs. baseline in GFR (\u22126%), RBF (\u221212%), and UNaV (\u221234%) were blunted vs. PL + l-NAME and LOS + l-NAME ( P &lt; 0.005), and the rise in U8-iso-PGF2\u03b1V was almost abolished (+37%, P &gt; 0.05 vs. baseline; P &lt; 0.01 vs. PL + l-NAME or LOS + l-NAME). We conclude that, since MANI blunted l-NAME-induced renal hemodynamic changes, CCs participate in the renal responses to NOSI in healthy, sodium-replete humans independent of changes in MAP and without the apparent contribution of the AT1R. Because the rise in U8-iso-PGF2\u03b1V was essentially prevented during MANI + l-NAME, CC blockade may oppose the renal effects of NOSI in part by counteracting oxidative stress responses to acutely impaired renal NO bioavailability.<\/jats:p>","DOI":"10.1152\/ajprenal.00568.2016","type":"journal-article","created":{"date-parts":[[2017,2,9]],"date-time":"2017-02-09T01:10:25Z","timestamp":1486602625000},"page":"F870-F878","source":"Crossref","is-referenced-by-count":2,"title":["Calcium channel blockade blunts the renal effects of acute nitric oxide synthase inhibition in healthy humans"],"prefix":"10.1152","volume":"312","author":[{"given":"Alberto","family":"Montanari","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Parma Medical School, Parma, Italy;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davide","family":"Lazzeroni","sequence":"additional","affiliation":[{"name":"Prevention and Rehabilitation Unit at the Don Gnocchi Foundation and Department of Clinical and Experimental Medicine, University of Parma Medical School, Parma, Italy; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanna","family":"Pel\u00e0","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Parma Medical School, Parma, Italy;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Crocamo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Parma Medical School, Parma, Italy;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuliya","family":"Lytvyn","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Musiari","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Parma Medical School, Parma, Italy;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aderville","family":"Cabassi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Parma Medical School, Parma, Italy;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David Z. 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