Montanari A, Lazzeroni D, Pelà G, Crocamo A, Lytvyn Y, Musiari L, Cabassi A, Cherney DZ. Calcium channel blockade blunts the renal effects of acute nitric oxide synthase inhibition in healthy humans. Am J Physiol Renal Physiol 312: F870–F878, 2017. First published February 8, 2017; doi:10.1152/ajprenal.00568. 2016.—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 g·kg1·min1 NG-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-PGF2V; an oxidative stress marker) were measured. With PL L -NAME, the following changes were observed: 6% MAP (P 0.005 vs. baseline), 10% GFR, 20% RBF, 49% UNaV (P 0.001), and 120% U8-iso-PGF2V (P 0.01). In contrast, MAP did not increase during LOS L-NAME or MANI L-NAME (P 0.05 vs. baseline), whereas renal changes were the same during LOS L-NAME vs. PL L-NAME (ANOVA, P 0.05). However, during MANI L-NAME, changes vs. baseline in GFR (6%), RBF (12%), and UNaV (34%) were blunted vs. PL L-NAME and LOS L-NAME (P 0.005), and the rise in U8-iso-PGF2V was almost abolished (37%, P 0.05 vs. baseline; P 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-PGF2V 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.
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