Mouse strains, sex, salt intake, AT1R activity and blood pressure

Abstract

Male C57Bl/6J mice are salt‐sensitive while male SJL/J mice are salt‐resistant which is related to the functional state of the renal dopamine D1 receptor (D1R). Angiotensin II may be involved in the decreased renal expression of D1R of salt‐sensitive obese Zucker rats. However, the roles of the duration and amount of dietary salt intake and sex on salt sensitivity are not well known. Therefore, we studied the effect of sodium intake (<0.009, 0.6, 0.8,1.6, 4, 6, % NaCl) on the blood pressure (BP), renal dopamine and angiotensin receptors and sodium transporters in three different strains of male and female mice. We found that 4 or 6% NaCl diet given for 1 or 3 wks increased the BP of male C57Bl/6Jackson but not C57Bl/6Taconic, Balb/c, or SJL/J mice. The male C57Bl/6J mice with NaCl intake equal to or greater than 1.6% had increased BP. Similar to that reported in male C57Bl/6J mice, the BP (telemetry) of female C57Bl/6J mice was also increased by 4% NaCl diet (1 wk) which is associated with a decrease in serum renin but an increase in renal protein expression of angiotensin type 1 (AT1R). The salt‐induced increase in BP was ameliorated by angiotensin type 1 (AT1R) blockade with candesartan (1 mg/kg/day, subcutaneously administered with osmotic mini‐pumps, 1 wk) in both sexes. Except for the lower body weight of female than male mice, as expected, there were no differences in food/water intake, urinary excretions of water and electrolytes, and serum concentrations of creatinine and electrolytes, regardless of diets. In female C57Bl/6J mice on 6% NaCl diet, candesartan increased renal D1R and D5R but not D2R, D3R, or D4R protein expression while male C57Bl/6J mice had increased renal D5R protein expression, only. There was a similar decrease in renal protein expressions of sodium‐hydrogen exchanger isoform 3, sodium‐potassium‐2 chloride cotransporter, sodium‐chloride cotransporter, and α, β and γ epithelial sodium channel (ENaC) but not type 2 sodium phosphate cotransporter and α1Na+K+ATPase, in both male and female mice. We conclude that the salt sensitivity of BP of C57BL6/J mice is not sex‐related. However, the amelioration of high salt induced‐hypertension by AT1R blockade may be mediated by the differential increase in renal dopamine receptor expression and similar reduction in renal apical sodium transporters, leading to a decrease in renal sodium transport in male and female mice.Support or Funding InformationThis work was supported in part by grants from the National Institutes of Health, HL68686, HL23081, HL074940, HL092196, and DK039308. Dr. Xiaoyan Wang was supported, in part, by National Kidney Foundation of Maryland (Professional Development Award, 2014).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.