Lowering of Sympathetic Burst Frequency in Post‐Pubertal Female but not Male Rats

Abstract

INTROCardiovascular disease (CVD) leads to an overall reduction in the quality of life and is the leading cause of mortality in the United States. The risk of CVD increases with age; however, women of reproductive age have a lower CVD prevalence. CVD is associated with elevations in sympathetic nerve activity, which has been analyzed in humans by quantifying sympathetic burst frequency. Whether sympathetic burst frequencies are different between pre‐ and post‐pubertal males and females is unknown.PURPOSEThe purpose of this study was to analyze sympathetic burst frequencies for potential differences between male and female rats.HYPOTHESISWe hypothesized that resting sympathetic burst frequency would be lower in post‐pubertal females compared to age‐matched males. We also predicted lower burst frequency in post‐ versus pre‐pubescent females.METHODSWe analyzed splanchnic nerve (SSNA) recordings from Inactin‐anesthetized male and female Sprague‐Dawley rats at 4‐weeks (pre‐pubertal) and 8‐ and 16‐weeks (post‐pubertal) of age. Sympathetic bursts were obtained by rectifying and integrating raw SSNA. Burst frequency was calculated using the Peak Parameters extension in LabChart software.RESULTSBurst frequency was higher in 4‐week (n=8) and 8‐week (n=9) old female rats compared to 16‐week old (n=6) female rats (5.6+1.2; 4.8+0.4 and 2.4+0.3 Hz, p<.001 and p=0.02, respectively). At 16 weeks of age, female rats also had a significantly lower burst frequency when compared to male rats (n=4) (2.4+0.3 vs, 4.8+0.4 Hz, respectively, p=0.01). Finally, there was no significant difference found in burst frequencies between male rats at any age (p>0.05 for all), suggesting sex‐dependent differences in the development of sympathoexcitation.CONCLUSIONPreliminary results suggest that following the onset of puberty in female rats, sympathetic burst frequency decreases over time, changes not seen in age‐matched male rats. Given CVD is significantly lower in premenopausal women, lower sympathetic nerve activity as a result of puberty may provide a mechanistic basis by which decreased sympathetic burst frequency protects against CVD. Future experiments may be conducted to explore other burst characteristics (e.g. burst amplitude and width), and the role of specific female sex hormones, to further understand sex‐dependent development of CVD.