Sex and age result in differential regulation of the renal thiazide-sensitive NaCl cotransporter and the epithelial sodium channel in angiotensin II-infused mice

Am J Nephrol. 2009;30(6):554-62. doi: 10.1159/000252776. Epub 2009 Oct 21.

Abstract

Background/aims: We determined the effects of age and sex on the blood pressure (BP) response to angiotensin II (Ang II) infusion and evaluated the potential mechanistic role of the thiazide-sensitive NaCl cotransporter (NCC) and the epithelial sodium channel (ENaC).

Methods: Male and female mice (approximately 3 or 21 months of age) were infused with Ang II or control for 7 days.

Results: Males had a greater BP response to Ang II, somewhat enhanced by aging. Mean systolic BPs (at 7 days) were (mm Hg): 161, 143, 172, and 157 in young male, young female, old male, and old female mice, respectively. Immunoblotting changes in the whole kidney that supported this BP profile included a 51 and 52% increase in NCC band density in the old females and old males (as compared to sex-respective controls) with Ang II infusion, while the young males and young females showed an increase of 40 and 0%, respectively. Young males also had a greater reduction in major bands of beta- and gamma-ENaC, than did young female mice. The natriuretic response to hydrochlorothiazide supported an increase in activity of NCC with Ang II in aged mice only.

Conclusions: Increased sensitivity to Ang II in aging and male mice may involve overactivity of NCC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aging / metabolism*
  • Angiotensin II / pharmacology*
  • Animals
  • Blood Pressure / drug effects
  • Diuretics / pharmacology
  • Epithelial Sodium Channels / metabolism*
  • Female
  • Hydrochlorothiazide / pharmacology
  • Hypertension, Renal / chemically induced
  • Hypertension, Renal / drug therapy
  • Hypertension, Renal / physiopathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Natriuresis / drug effects
  • Receptors, Drug / metabolism*
  • Sex Characteristics*
  • Sex Factors
  • Solute Carrier Family 12, Member 3
  • Symporters / metabolism*
  • Vasoconstrictor Agents / pharmacology

Substances

  • Diuretics
  • Epithelial Sodium Channels
  • Receptors, Drug
  • Scnn1b protein, mouse
  • Slc12a3 protein, mouse
  • Solute Carrier Family 12, Member 3
  • Symporters
  • Vasoconstrictor Agents
  • Hydrochlorothiazide
  • Angiotensin II