Submitted on March 12, 2009
Revised on August 26, 2009
Accepted on August 28, 2009
RENAL DOPAMINERGIC DEFECT IN C57BL/6J MICE
Crisanto S Escano1, Ines Armando1*, Xiaoyan Wang1, Laureano Asico1, Anabelle Pascua1, Yu Yang1, Zheng Wang1, Yuen-Sum Lau2, and Pedro A. Jose3
1 Children's National Medical Center
2 University of Houston
3 Georgetown University
* To whom correspondence should be addressed. E-mail: IArmando{at}cnmc.org.
The C57BL/6J mouse strain, the genetic background of many transgenic and gene knockout models, is salt-sensitive and resistant to renal injury. We tested the hypothesis that renal dopaminergic function is defective in C57BL/6J mice. On normal NaCl (0.8%, 1 week) diet, anesthetized and conscious (telemetry) blood pressures were similar in C57BL/6J and SJL/J mice. High NaCl (6%, 1 week) increased blood pressure (
30%) in C57BL/6J but not in SJL/J mice and urinary dopamine to greater extent in SJL/J than in C57BL/6J mice. Absolute and fractional sodium excretions were lower in SJL/J than in C57BL/6J mice. The blood pressure/natriuresis plot was shifted to the right in C57BL/6J mice. Renal expressions of D1-like (D1R and D5R) and AT1Rs were similar on normal salt but high salt increased D5R only in C57BL/6J. GRK4 expression was lower on normal but higher on high salt in C57BL/6J than in SJL/J mice. Salt increased the excretion of microalbumin and 8-isoprostane (oxidative stress marker) and degree of renal injury to a greater extent in SJL/J than in C57BL6/J mice. A D1-like receptor agonist increased sodium excretion while a D1-like receptor antagonist decreased sodium excretion in SJL/J but not in C57BL/6J mice. In contrast, parathyroid hormone had a similar natriuretic effect in both strains. These results show that defective D1-like receptor function is a major cause of salt-sensitivity in C57BL/6J mice, decreased renal dopamine production might also contribute. The relative resistance to renal injury of C57BL/6J may be a consequence of decreased production of reactive oxygen species.
