Researcher(s)
- Jessica Shields, Biological Sciences, University of Delaware
Faculty Mentor(s)
- Jody Greaney, Department of Health Behavior and Nutrition Sciences, University of Delaware
Abstract
Introduction: Patients with Cushing’s syndrome, a pathological condition characterized by hypercortisolism, exhibit blunted endothelium-dependent dilation (EDD). However, it remains unknown whether otherwise healthy adults with greater cortisol output, reflective of chronic hypothalamic-pituitary-adrenal (HPA) axis activation, also demonstrate reduced EDD. We hypothesized that nitric oxide (NO)-mediated EDD would be reduced in healthy adults with higher total salivary cortisol output compared to those with lower total output. Because cortisol triggers the release of free radicals, we also explored the role of oxidative stress in mediating this association. Methods: Nine healthy adults (8 females; 36±14 yrs) collected saliva samples 4 times per day for four consecutive days. Cortisol concentration was measured via luminescence immunoassay, and participants were dichotomized into “lower” and “higher” groups based on the median area-under-the-curve values (0.922 µg/dL; an index of total salivary cortisol output). Cutaneous vasodilation was separately assessed by laser-Doppler flowmetry in response to local heating alone (control) and with concurrent perfusion of 10 μM tempol (superoxide dismutase mimetic), each followed by perfusion of 15 mM NG-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor) via intradermal microdialysis. Results: There were no differences between groups in EDD (84.9±10.3 vs 81.9±21.8%CVCmax; p=0.40) or NO-mediated dilation (70.2±9.2 vs 64.8±23.7%; p=0.32). Tempol appeared to improve both EDD (81.9±21.8 control vs 95.9±3.4%CVCmax tempol; p=0.13) and NO-mediated dilation (64.8±23.7 control vs 85.0±7.8% tempol; p=0.12) in adults with higher cortisol output but not in those with lower output (both p>0.22). Conclusion: In healthy adults, greater total salivary cortisol output appears associated with superoxide-induced suppression of NO-mediated EDD. These data suggest that chronic HPA-axis activation may contribute to preclinical microvascular dysfunction through oxidative stress, a potential early mechanism linking cortisol exposure to future cardiometabolic risk.