Tiwari S, Li L, Riazi S, Halagappa VK, Ecelbarger CM
Sex differences in adaptive down-regulation of pre-macula densa sodium transporters with Ang II infusion in mice. [JOURNAL ARTICLE]
Am J Physiol Renal Physiol 2009 Nov 4.
An increase in blood pressure (BP) due to angiotensin II (Ang II) infusion or other means is associated with adaptive pressure natriuresis due to reduced sodium reabsorption primarily in proximal tubule (PT) and thick ascending limb (TAL). We tested the hypothesis that male and female mice would show differential response to Ang II infusion with regard to the regulation of the protein abundance of sodium transporters in the PT and TAL, and whether these responses would be modulated by aging. Young (~3 months) and old (~21 months) male and female mice were infused with Ang II @ 800 ng/kg*bw/min by osmotic minimpump for 7 days or received a sham operation. Ang II increased MAP, measured by radiotelemetry, significantly more in male mice of both ages (increased ~30-40 mm Hg), as compared to females (increased ~15-25 mm Hg). On day 1, MAP was also significantly increased in old mice, relative to young (p = 0.10). Ang II infusion was associated with a significant decline in plasma testosterone (to <30% of control male) in male mice, and rise in young female mice (to 478% of control female). No sex differences were found in the upregulation of the sodium hydrogen exchanger (NHE3) abundance on western blots observed with Ang II infusion, or the down-regulation of the sodium phosphate cotransporter (NaPi-2); however aging did impact on some of these changes. Male mice (especially young) also had significantly reduced levels of the TAL bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2 to 60% of male control), while young females showed an increase (to 126% of female control) with Ang II infusion. These sex differences do not support impaired pressure natriuresis in male mice, but might reflect a greater need and attempt to mount an appropriately BP-metered natriuretic response by additional down-regulation of TAL sodium reabsorption. Key words: RAAS, testosterone, hypertension, gender differences, NaPi-2.
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