Objective: The aim of this study was to determine whether changes in cardiac Na+,K(+)-ATPase subunits and Na+/Ca2+ exchanger expression are regulated in aldosterone-salt hypertensive guinea pigs.
Methods: Guinea pigs (GP) were unilaterally nephrectomized and randomized into three groups (aldosterone-salt; control-salt; control). After 90 days of treatment, echocardiographic M-mode assessment and right carotid arterial catheterization were performed in vivo, and plasma hormones and electrolytes were measured. mRNA and protein levels were studied by Northern and Western blot analysis.
Results: Aldosterone-salt treatment induced, (1) arterial hypertension (+40%) and LV hypertrophy (+60%) without altering LV-fractional shortening, (2) an increase in plasma norepinephrine levels (+262%) and suppression of renin activity. Northern blot analysis showed the presence of the mRNA encoding the three alpha isoforms and the beta 1 subunit of Na+,K(+)-ATPase in GP myocardium. In the aldosterone-salt group, levels of alpha 1 and beta 1 mRNAs were unchanged. alpha 2 mRNA was increased in both ventricles, whereas alpha 3 mRNA was increased in hypertrophied LV only. Furthermore, levels of the Na+/Ca2+ exchanger mRNA were decreased in both ventricles. At protein level, the two major transcripts (alpha 1 and alpha 2) were detected but alpha 3 isoform was not. Parallel changes in protein and mRNA accumulation of alpha 1 and alpha 2 isoforms were observed in hypertrophied LV.
Conclusion: These results show that alpha 1 and alpha 2 isoforms are expressed in GP heart and that they are independently regulated in aldosterone-salt hypertension. Like the alpha 1 isoform in renal tissue, alpha 2 isoform is the main target of aldosterone-salt. Reciprocal expression of the Na+/Ca2+ exchanger and Na+,K(+)-ATPase suggests an adaptational mechanism which maintains an appropriate sodium gradient and calcium concentration in hypertensive myocardium.