PMID- 21900450
OWN - NLM
STAT- MEDLINE
DCOM- 20120209
LR  - 20211203
IS  - 1522-1466 (Electronic)
IS  - 1522-1466 (Linking)
VI  - 302
IP  - 1
DP  - 2012 Jan 1
TI  - Defective nitric oxide production impairs angiotensin II-induced Na-K-ATPase 
      regulation in spontaneously hypertensive rats.
PG  - F47-51
LID - 10.1152/ajprenal.00270.2011 [doi]
AB  - Angiotensin (ANG) II via ANG II type 1 receptors (AT1R) activates renal sodium 
      transporters including Na-K-ATPase and regulates sodium homeostasis and blood 
      pressure. It is reported that at a high concentration, ANG II either inhibits or 
      fails to stimulate Na-K-ATPase. However, the mechanisms for these phenomena are 
      not clear. Here, we identified the signaling molecules involved in regulation of 
      renal proximal tubular Na-K-ATPase at high ANG II concentrations. Proximal 
      tubules from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats 
      were incubated with low concentrations of ANG II (pM), which activated 
      Na-K-ATPase in both the groups; however, the stimulation was more robust in SHR. 
      A high concentration of ANG II (muM) failed to stimulate Na-K-ATPase in WKY rats. 
      However, in SHR ANG II (muM) continued to stimulate Na-K-ATPase, which was 
      sensitive to the AT1R antagonist candesartan. In the presence of 
      N(G)-nitro-l-arginine methyl ester (l-NAME), a nitric oxide (NO) synthase (NOS) 
      inhibitor, ANG II (muM) caused stimulation of Na-K-ATPase in proximal tubules of 
      WKY rats while having no further stimulatory effect in SHR. ANG II (muM), via 
      AT1R, increased proximal tubular NO levels in WKY rats but not in SHR. In SHR, 
      NOS was uncoupled as incubation of proximal tubules with ANG II and l-arginine, a 
      NOS substrate, caused superoxide generation only in SHR and not in WKY rats. The 
      superoxide production in SHR was sensitive to l-NAME. There was exaggerated 
      proximal tubular AT1R-G protein coupling and NAD(P)H oxidase activation in 
      response to ANG II (muM) in proximal tubules of SHR compared with WKY rats. In 
      SHR, inhibition of NADPH oxidase restored NOS coupling and ANG II-induced NO 
      accumulation. In conclusion, at a high concentration ANG II (muM) activates renal 
      NO signaling, which prevents stimulation of Na-K-ATPase in WKY rats. However, in 
      SHR ANG II (muM) overstimulates NADPH oxidase, which impairs the NO system and 
      leads to continued Na-K-ATPase activation.
FAU - Javkhedkar, Apurva A
AU  - Javkhedkar AA
AD  - Univ. of Houston, 4800 Calhoun Rd., 521 SR 2 Bldg., Houston, TX 77204, USA.
FAU - Lokhandwala, Mustafa F
AU  - Lokhandwala MF
FAU - Banday, Anees Ahmed
AU  - Banday AA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110907
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Benzimidazoles)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Tetrazoles)
RN  - 11128-99-7 (Angiotensin II)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 94ZLA3W45F (Arginine)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 7.2.2.13 (Sodium-Potassium-Exchanging ATPase)
RN  - S8Q36MD2XX (candesartan)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
SB  - IM
MH  - Angiotensin II/*physiology
MH  - Animals
MH  - Arginine/metabolism
MH  - Benzimidazoles/pharmacology
MH  - Biphenyl Compounds
MH  - Kidney Tubules, Proximal/drug effects/*physiopathology
MH  - Male
MH  - NADPH Oxidases/metabolism
MH  - NG-Nitroarginine Methyl Ester/pharmacology
MH  - Nitric Oxide/*metabolism
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Rats, Inbred WKY
MH  - Receptor, Angiotensin, Type 1/metabolism
MH  - Sodium-Potassium-Exchanging ATPase/*metabolism
MH  - Tetrazoles/pharmacology
EDAT- 2011/09/09 06:00
MHDA- 2012/02/10 06:00
CRDT- 2011/09/09 06:00
PHST- 2011/09/09 06:00 [entrez]
PHST- 2011/09/09 06:00 [pubmed]
PHST- 2012/02/10 06:00 [medline]
AID - ajprenal.00270.2011 [pii]
AID - 10.1152/ajprenal.00270.2011 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2012 Jan 1;302(1):F47-51. doi: 
      10.1152/ajprenal.00270.2011. Epub 2011 Sep 7.