Mice lacking protein kinase C beta present modest increases in systolic blood pressure and NH4Cl-induced metabolic acidosis.
The conventional protein kinase C isoenzyme beta (PKC-beta) is expressed in various structures of mouse kidney. To get insights into the function, PKC-beta knockout (-/-) and wild-type (+/+) mice were studied. Under basal conditions, PKC-beta-/- mice exhibited a higher systolic blood pressure (in awake mice), normal plasma concentrations of Na+ and K+, and normal plasma pH. Urine osmolality and 24-hour excretion of fluid, Na+, K+ and albumin were not different between genotypes, but urine pH was more alkaline in PKC-beta-/- mice. Inulin clearance experiments under anesthesia confirmed a higher systolic blood pressure and revealed normal glomerular filtration rate and fractional excretion of fluid, Na+ and K+ in PKC-beta-/- mice. The ability to restrict renal Na+ excretion in response to a low Na+ diet was unaltered in PKC-beta-/- mice. Chronic acid loading (NH4Cl) did not affect blood pH in PKC-beta+/+ mice, but induced a modest metabolic acidosis in PKC-beta-/- mice. In conclusion, first evidence is presented that (i) PKC-beta contributes to the regulation of arterial blood pressure, and (ii) PKC-beta is required for normal acid-base balance, which may relate to its expression and function in intercalated cells of the collecting duct.
Yao
Li-Jun
LJ
Institute of Pharmacology and Toxicology, University of Tübingen, Tübingen, Germany.
Leitges
Michael
M
Vallon
Volker
V
D000138:Acidosis / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism*; D017398:Alternative Splicing; D000643:Ammonium Chloride / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000235:genetics*; D004232:Diuretics / Q000494:pharmacology; D007685:Kidney Tubules, Collecting / Q000201:enzymology; D051379:Mice; D018345:Mice, Knockout; D011493:Protein Kinase C / Q000235:genetics* / Q000378:metabolism; D064546:Protein Kinase C beta; D012982:Sodium, Dietary / Q000493:pharmacokinetics; D014851:Wakefulness
D004232:Diuretics; D012982:Sodium, Dietary; D000643:Ammonium Chloride; D011493:Protein Kinase C; D064546:Protein Kinase C beta