The sympathetic nervous system participates in both shortâ and longâterm cardiovascular regulation. The microneurographic technique, enabling in humans direct recordings from the populations of postâganglionic sympathetic neurons innervating the skeletal muscle vasculature (i.e. muscle sympathetic nerve activity; MSNA), has yielded key insights into mechanisms of sympathetic regulation of the circulation in health, and, importantly, its contributions to cardiovascular disease development and progression. Due to its invasive nature, as well as the technical challenges involved in site acquisition and burst quantification, its application has been limited primarily to trained investigators studying small, selected cohorts, rather than populations. In healthy individuals, MSNA burst frequency or burst incidence, as measured under supine resting conditions, exhibit considerable interâindividual variability, yet are highly reproducible within individuals over time. However, such variability, as well as the limited data, has impaired the establishment of ageâ and sexâdependent normative values. Therefore, we aimed to develop resting MSNA reference charts, representing MSNA percentile curves, in a large cohort of young and older men and women. Specifically, we retrospectively assembled a dataset of 654 healthy, unmedicated normotensive (<140/90 mmHg) individuals from four participating Canadian laboratories, including 396 men (aged 18â71 yrs) and 258 women (aged 18â81 yrs), in whom baseline resting MSNA was evaluated over a minimum of 5 min. Quantile regression was used to estimate the 5th, 20th, 50th (i.e. median), 80th, and 95th percentiles for resting MSNA burst frequency and burst incidence in men and women as a function of age. Quantiles were parameterized as functions of age by both a oneâ and twoâterm fractional polynomial model with power selected from a ladder of values (i.e. â2, â1, â0.5, 0.5, 1, 2, 3). Next, an iterative fitting approach was applied to the MSNA versus age data to determine the fractional coefficients and the combination of values for the two powers from the ladder that provided the greatest goodness of fit (i.e. lowest Ï2). The 5th, 20th, 50th, 80th, and 95th percentiles for MSNA burst frequency and burst incidence in men and women as a function of age are displayed in the figure below. In conclusion, these MSNA percentile curves, developed from a large sample of men and women, provide ageâ and sexârelated reference values for resting MSNA levels in healthy, normotensive individuals, and, furthermore, by establishing 95% confidence limits, may help inform comparative studies of disease states referenced to ageâ and sexâmatched controls.Figure 1