In vivo stimulation of AMP-activated protein kinase enhanced tubuloglomerular feedback but reduced tubular sodium transport during high dietary NaCl intake.
AMP-activated protein kinase (AMPK) is expressed in the apical membrane of cortical thick ascending limb, distal, and collecting tubules as well as macula densa cells of the kidneys. AMPK is an active modulator of epithelial Na(+) channels, Na(+)-2Cl(-)-K(+) cotransporter, and the ATP-dependent potassium channel. The present experiments explored whether AMPK participates in the regulation of tubuloglomerular feedback (TGF) and renal tubular sodium handling. To this end, renal clearance and micropuncture experiments were performed in anesthetized rats. Under normal NaCl diet, neither TGF response nor renal fluid and sodium excretion were altered by pharmacological activation of AMPK in vivo. However, under high NaCl diet, the TGF response was significantly enhanced after intravenous or intratubular application of the AMPK activator AICAR. Moreover, AICAR application significantly increased fractional delivery of fluid and sodium to the end of the proximal tubule. High dietary NaCl intake increased the renal transcript levels encoding the AMPK-alpha1 subunit, while it decreased the expression of AMPK-beta1 and AMPK-gamma2 subunits. Immunoblots revealed that high dietary NaCl intake reduced renal expression of activated AMPK by about three times compared to normal NaCl diet whereas additional AICAR application increased AMPK activity. Our results suggest that AMPK regulates tubuloglomerular balance as well as tubular transport upon change of renal work load.
Huang
Dan Yang
DY
Department of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard-Karls-University Hospitals and Clinics, and Interfaculty Centre of Pharmacogenomics and Pharmaceutical Research, University of Tübingen, Wilhelmstr. 56, 72074, Tübingen, Germany. danyang.huang@uni-tuebingen.de
Gao
Huanhuan
H
Boini
Krishna M
KM
Osswald
Hartmut
H
Nürnberg
Bernd
B
Lang
Florian
F
D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D000818:Animals; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000008:administration & dosage; D025461:Feedback, Physiological; D006439:Hemodynamics; D017136:Ion Transport; D007678:Kidney Glomerulus / Q000187:drug effects / Q000201:enzymology*; D007684:Kidney Tubules / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012265:Ribonucleotides / Q000008:administration & dosage; D012964:Sodium / Q000378:metabolism* / Q000652:urine; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000378:metabolism*; D014563:Urodynamics; D014882:Water-Electrolyte Balance / Q000187:drug effects
D020536:Enzyme Activators; D012333:RNA, Messenger; D012265:Ribonucleotides; D017673:Sodium Chloride, Dietary; D000620:Aminoimidazole Carboxamide; D012964:Sodium; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide