Swim training increases ventricular atrial natriuretic factor (ANF) gene expression as an early adaptation to chronic...

Increased ventricular ANF-mRNA is observed as a compensating mechanism in response to many forms of overload including chronic exercise. It is unknown if exercise-induced increases in ANF expression are mediated at the transcriptional level and whether specific cis-element(s) may be involved. To study this, rats were injected with several different ANF reporter plasmids. Following recovery, the animals were made to swim for 60 minutes per day. One week of swim training significantly increased plantaris muscle cytochrome oxidase activity and left ventricular ANF-mRNA levels. Exercise training significantly increased ANF reporter expression. We have previously demonstrated that a single cis-element (POE) mediates pressure overload activation of ANF expression during developing hypertrophy. Site-specific mutation of the POE cis-element (-495/-489) within the ANF promoter also ablated exercise-induced increases in reporter expression indicating that the POE site was critical. Further, exercise increase the expression of a POE-heterologous construct, indicating that the POE cis-element alone was sufficient for exercise induced activation. Gel mobility shift analysis, using the POE cis-element as a probe, determined that a single complex was formed and that training did not influence the DNA-protein binding pattern. These results indicate that increased ANF expression is mediated at the transcriptional level as an early adaptation to chronic exercise. The same cis-element that mediated pressure-overload activation of ANF reporter expression was also found to be critical and sufficient to mediate exercise-induced increases in ANF reporter expression. These findings suggest that there may be some overlap in the response to physiological and pathological forms of overload during the phase of developing hypertrophy.