PMID- 28179255
OWN - NLM
STAT- MEDLINE
DCOM- 20170807
LR  - 20211204
IS  - 1522-1466 (Electronic)
IS  - 1522-1466 (Linking)
VI  - 312
IP  - 5
DP  - 2017 May 1
TI  - Calcium channel blockade blunts the renal effects of acute nitric oxide synthase 
      inhibition in healthy humans.
PG  - F870-F878
LID - 10.1152/ajprenal.00568.2016 [doi]
AB  - 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 mug.kg(-1).min(-1) 
      N(G)-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-PGF2alphaV; 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-PGF2alphaV (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-PGF2alphaV 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-PGF2alphaV 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.
CI  - Copyright (c) 2017 the American Physiological Society.
FAU - Montanari, Alberto
AU  - Montanari A
AD  - Department of Clinical and Experimental Medicine, University of Parma Medical 
      School, Parma, Italy; alberto.montanari@unipr.it.
FAU - Lazzeroni, Davide
AU  - Lazzeroni D
AD  - Prevention and Rehabilitation Unit at the Don Gnocchi Foundation and Department 
      of Clinical and Experimental Medicine, University of Parma Medical School, Parma, 
      Italy; and.
FAU - Pela, Giovanna
AU  - Pela G
AD  - Department of Clinical and Experimental Medicine, University of Parma Medical 
      School, Parma, Italy.
FAU - Crocamo, Antonio
AU  - Crocamo A
AD  - Department of Clinical and Experimental Medicine, University of Parma Medical 
      School, Parma, Italy.
FAU - Lytvyn, Yuliya
AU  - Lytvyn Y
AD  - Division of Nephrology, University Health Network, University of Toronto, 
      Toronto, Ontario, Canada.
FAU - Musiari, Luisa
AU  - Musiari L
AD  - Department of Clinical and Experimental Medicine, University of Parma Medical 
      School, Parma, Italy.
FAU - Cabassi, Aderville
AU  - Cabassi A
AD  - Department of Clinical and Experimental Medicine, University of Parma Medical 
      School, Parma, Italy.
FAU - Cherney, David Z I
AU  - Cherney DZI
AD  - Division of Nephrology, University Health Network, University of Toronto, 
      Toronto, Ontario, Canada.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20170208
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Biomarkers)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Dihydropyridines)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Nitrobenzenes)
RN  - 0 (Piperazines)
RN  - 27415-26-5 (8-epi-prostaglandin F2alpha)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 6O4754US88 (manidipine)
RN  - B7IN85G1HY (Dinoprost)
RN  - JMS50MPO89 (Losartan)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
SB  - IM
MH  - Adult
MH  - Arterial Pressure/drug effects
MH  - Biomarkers/urine
MH  - Calcium Channel Blockers/*administration & dosage
MH  - Dihydropyridines/*administration & dosage
MH  - Dinoprost/analogs & derivatives/urine
MH  - Enzyme Inhibitors/*administration & dosage
MH  - Female
MH  - Glomerular Filtration Rate/drug effects
MH  - Healthy Volunteers
MH  - Hemodynamics/*drug effects
MH  - Humans
MH  - Infusions, Intravenous
MH  - Kidney/*blood supply/*drug effects/enzymology
MH  - Losartan/*administration & dosage
MH  - Male
MH  - NG-Nitroarginine Methyl Ester/*administration & dosage
MH  - Natriuresis/drug effects
MH  - Nitric Oxide/*antagonists & inhibitors/metabolism
MH  - Nitrobenzenes
MH  - Oxidative Stress/drug effects
MH  - Piperazines
MH  - Renal Circulation/*drug effects
MH  - Time Factors
OTO - NOTNLM
OT  - NG-nitro-l-arginine methyl ester
OT  - losartan
OT  - manidipine
OT  - nitric oxide
OT  - renal hemodynamic function
EDAT- 2017/02/10 06:00
MHDA- 2017/08/08 06:00
CRDT- 2017/02/10 06:00
PHST- 2016/10/20 00:00 [received]
PHST- 2017/02/01 00:00 [revised]
PHST- 2017/02/06 00:00 [accepted]
PHST- 2017/02/10 06:00 [pubmed]
PHST- 2017/08/08 06:00 [medline]
PHST- 2017/02/10 06:00 [entrez]
AID - ajprenal.00568.2016 [pii]
AID - 10.1152/ajprenal.00568.2016 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2017 May 1;312(5):F870-F878. doi: 
      10.1152/ajprenal.00568.2016. Epub 2017 Feb 8.