Despite both sexes seeing an increase in risks for cardiovascular disease as they age, women typically see a sharper one, and the gap between men and woman continues to increase. Cholesterol and weight increase only account for 50% of the age-related increases in risk. Thus this study looked at the sympathetic nervous system and its role in the development of age-related cardiovascular disease. At the time of the study, little was known about the effects of sex-differences on age-related sympathetic outflow, and this seems to be the case today. However, this study provided a good foundation for researchers to continue to investigate the role of sympathetic outflow on age-related blood pressure changes and cardiovascular disease development.
The study looked at the sympathetic outflow, blood pressure, and heart rate in “normal” white subjects from ages 20 to 72. They examined the influence of age on the interaction between sympathetic outflow and blood pressure. They also looked at the influence of menopause on sympathetic outflow. They hypothesized that aging will have a more significant impact on sympathetic outflow in women versus men.
Intraneural measurements of muscle sympathetic nerve activity (MSNA) were taken from the peroneal nerve. Blood pressure and heart rate were also measured. MSNA was recorded as bursts per minute, and only those that achieved a minimum signal-to-noise ratio of 3:1 were counted. Mean blood pressure was taken every minute, and rate heart was measured by an electrocardiogram. Regression slopes were made to analyze the interaction between age and gender. Effects of age on MSNA were evaluated by 2-way analysis of variance with the decade of life each subject was in and gender as the groups.
MSNA correlated with age in both genders. However, MSNA had a far stronger correlation in women (r=0.73; P<0.0001) versus men (r= 0.31; P=0.003). Age explained 53% of MSNA variance in females but only 8% in men. As the subjects aged, there were increases in MSNA bursts for both sexes. However, women saw a greater increase for every decade aged compared to men (6.5 bursts/min versus 2.6 bursts/min; similar results when compared at bursts/100 heart beats).
MSNA was lower in females than males for younger subjects. As the subjects aged, the age-related increase in MSNA was greater in females than in males. The interaction of sex and age was significant, suggesting that the effect age has on MSNRA is sex-dependent. Premenopausal and postmenopausal women within the same decade of age had similar MSNA, indicating no relationship between menopause and MSNA.
Blood pressure and MSNA was not related in young subjects. However, there was a correlation in both male and female subjects above the age of 40. For these older individuals, every 10-burst/min increase in MSNA in women showed a rise of 6.1 mmHg in their blood pressure, versus a 2.7 mmHg in men.
The study was able to demonstrate a higher possible correlation between aging and an increase in sympathetic outflow in white women over white men. They also found that menopause does not explain the age-related increase in sympathetic outflow in women. Finally, they found a positive interaction between blood pressure and MSNA for people over 40 years of age. MSNA increased at a rate of 2.5-times higher in women than in men. Age contributed to the MSNA variance 6 times greater in women than in men. These results were consistent with previous studies done in Japanese subjects that showed MSNA was lower in younger women than in younger men and similar amongst the older subjects, suggesting that their results are not race-dependent (although, I disagree, because they only looked at individuals from a few, small populations located in particular parts of the world. They did not include other races aside from White Americans or Japanese individuals in their current or past studies, and thus their results cannot be said to be “race-independent”).
The significant correlation between MSNA and blood pressure provided support for the role of sympathetic activation in the link between aging and hypertension. This is more relevant in women than in men. However, the at the time of the study, the mechanisms that lead to the sex-differences between MSNA and blood pressure were unknown. They suggested that hypertension initially arises from an increased sympathetic output at the developing stages of the disease. As subjects age, they suggested that the increased sympathetic outflow leads to an age-related decrease in compliance as subjects age.
Despite their results suggesting that menopause does not contribute to age-related increases in MSNA, they were unable to show that female sex hormones do not contribute to the lower blood pressure and MSNA measured in younger subjects. However, the results from this study provided a solid foundation for other researchers to examine the role of female sex hormones in the alteration of sympathetic outflow, much like what we are starting to do in our lab.
I chose to look at a human study this week because I felt that it was necessary to see why we are studying sex-differences in RVLM activation. Although we study rats, we are not looking to solve the physiological problems in animal models. We hope that our results will translate to humans so that we can better understand the sex-differences that play a possible role in altering sympathetic activation and hypertension in our bodies. The study that I reviewed this week provided a substantial starting point for research in the hypertension field. The researchers examined a hypertensive, sex-dependent, external phenotype and were left wondering about the underlying mechanisms. Thus, the animal studies that followed are essential to solve those remaining questions. We cannot look at the neuronal components of this pathway in human subjects. Therefore, we look at rats. However, we still see results in animals similar to those in human subjects, such as changes in blood pressure and sympathetic outflow. Studies like the one reviewed today help to verify that the results we are producing in animal models are translatable back to human subjects.
-O. Flessland
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