Sex Differences and Inactivity In Rats Determine the Progression of Increased Sympathetic Activity Over Time.

Abstract

Cardiovascular disease (CVD) is the leading cause of death, with males having a higher risk than females; that is, until menopause, when the risks reverse. Risk factors for CVD include a sedentary lifestyle as well as elevated sympathetic nerve activity (SNA). In women, resting SNA is influenced by the menstrual cycle; however, the interaction between sedentary conditions and the presence or absence of the female reproductive cycle on baseline sympathetic nerve activity is unknown. Therefore, the purpose of this study was to determine the effects of sedentary versus active conditions on resting SNA in male and female rats over time. In particular, we studied rats at four and eight weeks of age (i.e. before and after the onset of the estrous cycle, respectively in female rats). We hypothesized that time‐dependent increases in SNA in sedentary male rats would be offset by four weeks of voluntary exercise (running wheels) and attenuated in sedentary female rats due to the onset of the estrous cycle. We recorded splanchnic SNA from 32 rats under Inactin anesthesia and determined SNA action potential frequency according to Tan et al., (2009). Using a two‐way analysis of variance (ANOVA), with sex and condition as main effects, we found that four week‐old male rats exhibited lower SNA compared to eight week‐old sedentary males (42.0 ±6.3 Hz vs. 62.4 ±5.8 Hz; p=0.015; n=6 each), while exhibiting no significant difference from eight week‐old active males (37.4 ±6.1 Hz; p=0.003; n=7). In contrast, SNA was not significantly different between four week‐old females (54.6 ±4.5 Hz; n=4) and eight week‐old sedentary females (46.0 ±4.3 Hz; p=0.348; n=5), suggesting a lack of inactivity‐related increases in SNA as observed in males. SNA in four week‐old females was also not significantly different than eight week‐old active females (51.0 ±5.8 Hz; p=0.708; n=4). Our results suggest a sedentary lifestyle promotes increases in SNA over time in males but not females, due to physical inactivity in males and a protective effect of ovarian hormones in females. Male sex‐ and inactivity‐dependent increases in SNA likely play an important role in the higher risks of CVD observed in males compared to females.Support or Funding Information(NIH HL096787‐08; AHA25810010)