Arrhythmogenic effect of androgens on the rat heart.

In most species androgens shorten the cardiac action potential and reduce the risk of afterdepolarizations. Despite the central role of the rat model in physiological studies, the effects of androgens on the rat heart are still inconclusive. We therefore performed electrophysiological studies on the perfused rat right ventricular free wall. We found a correlation between androgenic activity and a propensity to generate ventricular ectopic action potentials. We also found that the testosterone treatment increased action potential duration at 90 % of repolarization (APD90), while androgenic inhibition increased the time to peak and decreased APD90. We observed that the voltage-gated potassium channel Kv4.3 and the bi-directional membrane ion transporter NCX in the rat myocardium were regulated by androgenic hormones. One possible explanation for these findings is that due to the expression of specific ion channels in the rat myocardium, the action potential response to its hormonal background is different from those described in other experimental models. Our results indicate that androgenic control of NCX expression plays a key role in determining arrhythmogenicity in the rat heart.

Decreased NHE8 isoform expression and defective acidification in proximal convoluted tubules of senile rats.

We have previously found that aged rats show decreased proximal acidification without changes in NHE3 or V-H(+) ATPase expression in brush border membrane vesicles. However, we did not identify any mechanism underlying these observations. The aim of the present work was to evaluate some of the regulatory systems of proximal acidification that could be affected by aging. We measured plasma concentrations of parathyroid hormone (PTH) and the amount of cAMP in the renal cortex of young and old Wistar rats. PTH plasma concentration was increased in old rats, whereas, although it showed a tendency to increase, the cAMP content in the renal cortex of old rats was not significantly different compared with the cortex of young rats. We measured the abundance of NHE8 isoforms of the Na(+)/H(+) exchanger in brush border membrane vesicles from proximal convoluted tubules (PCT) of young and old rats by western blot analysis. We performed RT-PCR experiments in renal cortex homogenates from both experimental groups to evaluate mRNA expression of NHE3, NHE8 and H(+)ATPase. In senile rats, we detected a decreased abundance (at both gene expression and protein level) of the NHE8 isoform. These results could explain previous observations in which proximal tubule acidification appears affected in aged rats through a decrease in the activity of ethylisopropyl amiloride (EIPA)- and Bafilomycin-sensitive components, without changes in the NHE3 and V-H(+)ATPase abundance in the apical membrane of the PCT.