LAUSR

Male aging is associated with a general decline in serum testosterone (T) concentrations. Low endogenous T is associated with increased cardiovascular disease risk, and we recently demonstrated accelerated age-related endothelial dysfunction, measured by brachial artery flow mediated dilation (FMD), in middle-aged/older (MA/O) men with low T compared with age-matched men with normal T. Endothlin-1 (ET-1) is a potent vasoconstrictor that is modulated by sex hormones and contributes to age-associated endothelial dysfunction. However, whether ET-1 contributes to reduced FMD in MA/O men with low T has yet to be determined. PURPOSE: to determine if ET-1 contributes to reduced FMD in MA/O men with low T. HYPOTHESIS: we hypothesized that MA/O men with low T would have higher ET-1 concentrations compared with young and MA/O men with normal T. Additionally, we hypothesized that there would be an inverse relation between ET-1 and FMD. METHODS: 60 men were categorized as either young (18-40 years, T: 400-1000 ng/dL) or MA/O (50-75 years) with low (<300ng/dL) or normal (400-1000 ng/dL) serum total T. T was determined from a venous blood draw using a one-step competitive enzyme linked immunosorbent assay. Endothelial function was determined using brachial artery FMD and ET-1 concentrations were determined using radioimmunoassay from a venous blood sample. RESULTS: T concentrations were significantly lower in MA/O men with low T (269±48 ng/dL) compared to young (500±58 ng/dL; p<0.001) or MA/O men with normal T (512±115, ng/dL; p<0.001). There was no difference in T between MA/O men with normal T and young men (p=0.995). MA/O men were similar in age (low T=59±8, normal T=60±6 years; p=0.996) and older than young men (29±4 years; p<0.001 compared to MA/O with both low and normal T). Age-associated reductions in FMD (young=7.3±1.3 vs. MA/O normal T=5.7±2.2%; p=0.019), were exaggerated in MA/O men with low T (4.0±1.7%; p=0.010 vs. MA/O normal T, p<0.001 vs. young). ET-1 concentrations were similar between young and MA/O men with normal T (young= 5.6±0.9 vs. MA/O normal T=6.0±1.4 pg/mL; p=0.768), and higher in MA/O men with low T (7.7±2.8 pg/mL; p=0.002 vs. young, p=0.016 vs. MA/O normal T). There was a moderate inverse association between FMD and ET-1 (r=-0.374, p=0.003). CONCLUSIONS: These data suggest that the greater age-associated endothelial dysfunction in MA/O men with low T may be related to elevations in ET-1. Future studies should examine the effects of low T on endothelin receptors ETA and ETB, as well as factors that could explain the increase in ET-1 in MA/O men with low T. Supported by NIH Grants R01AG049762, U54AG062319, and T32AG000279-16A1 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.