Gonadectomy of adult male Dark Agouti and Copenhagen rats abolishes phenotypic differences in cardiovascular regulation.

The Dark Agouti (DA) rat has superior treadmill running capacity relative to the Copenhagen (COP) rat. The disparity in running capacity is associated with differences in neural control of the cardiovascular system. These intermediate phenotypes may be causative of the differences in running capacity but it remains unclear what mechanism may be responsible for these differences. One mechanism may be testosterone levels and its effects on the cardiovascular system. Previous reports have demonstrated that testosterone can alter calcium regulatory protein expression patterns and directly increase ventricular myocyte contractility. In addition, testosterone has been shown to increase cardiac sympathetic innervation and baroreflex control in a manner that would favor increased exercise capacity. Thus, the divergent exercise capacity phenotype of DA and COP rats may involve testosterone and its effect on the cardiovascular and autonomic nervous system. We predict testosterone levels will be higher in the DA rat and cardiac sympathetic tonus (ST) will be proportional to basal testosterone levels in both the DA and COP rat. Intact and castrated male DA and COP rats were used to compare cardiac ST in relation to testosterone levels. The intact DA rats have a significantly higher cardiac ST. Castration is associated with a 23% and 10% decrease in ST in the DA and COP rats respectively. Importantly, there is no difference in cardiac ST in DA and COP rats after castration. These results suggest testosterone levels may be a phenotype that is contributing to both exercise capacity and the intermediate phenotypic difference in cardiac ST.