Changes in brain Na, K-ATPase isoform expression and enzymatic activity after aortic constriction

Abstract

The objective of the present study was to test the hypothesis that brain Na, K-ATPase expression and/or activity is altered following an increase in blood pressure produced by constriction of the abdominal aorta just proximal to the renal arteries. A suprarenal constriction (SRC) was made to conform to the diameter of a 19-gauge (19-G) or 20-gauge (20-G) needle, while in a sham-operated group (Sham) the aorta was exposed surgically but not constricted. Within 1 week of SRC, mean arterial pressure was increased and remained elevated at 4 weeks post surgery. At 1 week, whole-brain Na, K-ATPase mRNA levels were depressed for all isoforms (α1∼β1>α2>α3). No changes were observed in the hypothalamus. At 4 weeks, the mRNA levels of all α isoforms were significantly increased in the whole brain and these changes were paralleled by an increase of α2 and α3 transcript in the hypothalamus. β1 mRNA expression was increased in the hypothalamus only. The α-isoform protein expression generally changed in the same direction as mRNA changes at both 1 and 4 weeks, as did α1 enzyme activity at 1 week and the combined α2/α3 enzyme activities at 4 weeks. Since inhibition of brain Na, K-ATPase increases sympathetic nervous system (SNS) activity and blood pressure, the decreases in brain Na, K-ATPase expression and activity at 1 week post SRC may contribute to the hypertension during its developmental phase, while the increase in the α2/α3 brain expression and activity at 4 weeks may be a compensatory response to established hypertension.