Kidney function in mice lacking aldosterone.
To explore the effects of decreased amounts or absence of aldosterone, we have disrupted the gene coding for aldosterone synthase (AS) in mice and investigated blood pressure and kidney function in AS+/+, AS+/-, and AS-/- mice. AS+/- mice have normal blood pressures and show no abnormalities in electrolytes or kidney gene expression, but they have significantly higher than normal urine volume and lower urine osmolality. In contrast, the AS-/- mice have low blood pressure, abnormal electrolyte homeostasis (increased plasma concentrations of K+, Ca2+, and Mg2+ and decreased concentrations of HCO3(-) and Cl- but no difference in the plasma Na+ level), and disturbances in water metabolism (higher urine output, decreased urine osmolality, and impaired urine concentrating and diluting ability). Absence of aldosterone in the AS-/- mice induced several compensatory changes: an increased food intake-to-body weight ratio, an elevated plasma concentration of glucocorticoids, and strong activation of the renin-angiotensin system. Parallel with the markedly increased synthesis and release of renin, the AS-/- mice showed increased expression of cyclooxygenase-2 (COX-2) in macula densa. On salt supplementation, plasma electrolyte concentrations and kidney renin and COX-2 levels became similar to those of wild-type mice, but the lower blood pressure of the AS-/- mice was not corrected. Thus absence of aldosterone in AS-/- mice results in impairment of Na+ reabsorption in the distal nephron, decreased blood pressure, and strong renin-angiotensin system activation. Our data show the substantial correction of these abnormalities, except the low blood pressure, by high dietary salt does not depend on aldosterone.
Makhanova
Natalia
N
Dept. of Pathology & Laboratory Medicine, Univ. of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7525, USA.
Lee
Gene
G
Takahashi
Nobuyuki
N
Sequeira Lopez
Maria L
ML
Gomez
R Ariel
RA
Kim
Hyung-Suk
HS
Smithies
Oliver
O
D000136:Acid-Base Equilibrium; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics / Q000378:metabolism; D004573:Electrolytes / Q000097:blood / Q000652:urine; D006706:Homeostasis; D007022:Hypotension / Q000503:physiopathology*; D007668:Kidney / Q000473:pathology / Q000502:physiology* / Q000503:physiopathology; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009929:Organ Size; D012083:Renin / Q000378:metabolism
D004573:Electrolytes; D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2; D012083:Renin