Potassium Supplementation Prevents Sodium Chloride Cotransporter Stimulation During Angiotensin II Hypertension.
Angiotensin II (AngII) hypertension increases distal tubule Na-Cl cotransporter (NCC) abundance and phosphorylation (NCCp), as well as epithelial Na(+) channel abundance and activating cleavage. Acutely raising plasma [K(+)] by infusion or ingestion provokes a rapid decrease in NCCp that drives a compensatory kaliuresis. The first aim tested whether acutely raising plasma [K(+)] with a single 3-hour 2% potassium meal would lower NCCp in Sprague-Dawley rats after 14 days of AngII (400 ng/kg per minute). The potassium-rich meal neither decreased NCCp nor increased K(+) excretion. AngII-infused rats exhibited lower plasma [K(+)] versus controls (3.6±0.2 versus 4.5±0.1 mmol/L; P<0.05), suggesting that AngII-mediated epithelial Na(+) channel activation provokes K(+) depletion. The second aim tested whether doubling dietary potassium intake from 1% (A1K) to 2% (A2K) would prevent K(+) depletion during AngII infusion and, thus, prevent NCC accumulation. A2K-fed rats exhibited normal plasma [K(+)] and 2-fold higher K(+) excretion and plasma [aldosterone] versus A1K. In A1K rats, NCC, NCCpS71, and NCCpT53 abundance increased 1.5- to 3-fold versus controls (P<0.05). The rise in NCC and NCCp abundance was prevented in the A2K rats, yet blood pressure did not significantly decrease. Epithelial Na(+) channel subunit abundance and cleavage increased 1.5- to 3-fold in both A1K and A2K; ROMK (renal outer medulla K(+) channel abundance) abundance was unaffected by AngII or dietary K(+) In summary, the accumulation and phosphorylation of NCC seen during chronic AngII infusion hypertension is likely secondary to potassium deficiency driven by epithelial Na(+) channel stimulation.
From the Department of Cell and Neurobiology, Keck School of Medicine of USC, Los Angeles, CA.
Luciana C
LC
Veiras
From the Department of Cell and Neurobiology, Keck School of Medicine of USC, Los Angeles, CA.
Jiyang
J
Han
From the Department of Cell and Neurobiology, Keck School of Medicine of USC, Los Angeles, CA.
Donna L
DL
Ralph
From the Department of Cell and Neurobiology, Keck School of Medicine of USC, Los Angeles, CA. mcdonoug@usc.edu.
Alicia A
AA
McDonough
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007262:Infusions, Intravenous; D007677:Kidney Function Tests; D008297:Male; D015999:Multivariate Analysis; D010766:Phosphorylation; D011191:Potassium Deficiency / Q000517:prevention & control; D017419:Potassium, Dietary / Q000378:metabolism / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D049992:Sodium Chloride Symporters / Q000187:drug effects / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D014882:Water-Electrolyte Balance / Q000502:physiology*
D053503:Epithelial Sodium Channels; D017419:Potassium, Dietary; D049992:Sodium Chloride Symporters; D017923:Sodium-Hydrogen Exchangers; D000804:Angiotensin II
aldosterone-sensitive distal nephron; angiotensin II hypertension; dietary potassium; hypokalemia; kaliuresis