Cyclo-oxygenase-2 inhibition and endothelium-dependent vasodilation in younger vs. older healthy adults.

AIM: A major feature of endothelial dysfunction is reduced endothelium-dependent vasodilation, which in ageing may be due to decreased production of endothelial prostacyclin, or nitric oxide (NO), or both. METHOD: We tested this hypothesis in 12 younger (age 18-38 years, six women) and 12 older healthy adults (age 55-73 years, six post-menopausal women). Endothelium-dependent vasodilation was assessed by the forearm vascular conductance (FVC) response to intra-arterial acetylcholine (ACh) (0.5, 1.0, 2.0, 4.0 µg dl(-1) forearm tissue min(-1) ) before and 90 min after inhibition of the enzyme cyclo-oxygenase-2 (COX-2) with oral celecoxib (400 mg), followed by the addition of endothelial NO synthase inhibition with intra-arterial N(G) -monomethyl-l arginine acetate (L-NMMA). RESULTS: Ageing was associated with a significantly reduced FVC response to ACh (P = 0.009, age-by-dose interaction; highest dose FVC ± SEM in ageing: 11.2 ± 1.4 vs. younger: 17.7 ± 2.4 units, P = 0.02). Celecoxib did not reduce resting FVC or the responses to ACh in any group. L-NMMA significantly reduced resting FVC and the responses to ACh in all groups, and absolute FVC values following L-NMMA were similar between groups. CONCLUSION: In healthy normotensive younger and older adults, there is minimal contribution of prostacyclin to ACh-mediated vasodilation, yet the NO component of vasodilation is reduced with ageing. In the clinical context, these findings suggest that acute administration of medications that inhibit prostacyclin (i.e. COX-2 inhibitors) evoke modest vascular consequences in healthy persons. Additional studies are necessary to test whether chronic use of COX-2 medications reduces endothelium dependent vasodilation in older persons with or without cardiovascular risk factors.

Dietary sodium influences the effect of mental stress on heart rate variability: a randomized trial in healthy adults.

BACKGROUND: Dietary sodium influences intermediate physiological traits in healthy adults independent of changes in blood pressure. The purpose of this study was to test the hypothesis that dietary sodium affects cardiac autonomic modulation during mental stress. METHOD: In a prospective, randomized cross-over design separated by 1 month between diets, 70 normotensive healthy young adults (F/M: 44/26, aged 18-38 years) consumed a 5-day low (10 mmol/day), normal (150 mmol), and high (400 mmol) sodium diet followed by heart rate variability (HRV) recordings at rest and during 5-min computerized mental arithmetic. Women were studied in the low hormone phase of the menstrual cycle following each diet. RESULTS: Diet did not affect resting blood pressure, but heart rate (HR) (mean ± SE) was 66 ± 1, 64 ± 1, and 63 ± 1 bpm in low, normal, and high sodium conditions, respectively (analysis of variance P = 0.02). For HRV, there was a main effect of sodium on resting SD of normalized RR intervals (SDNN), square root of the mean squared difference of successive normalized RR intervals (RMSSD), high frequency, low-frequency normalized units (LFnu), and high-frequency normalized units (HFnu) (P < 0.01 for all). The response to low sodium was most marked and consistent with sympathetic activation and reduced vagal activity, with increased LFnu and decreased SDNN, RMSSD, and HFnu compared to both normal and high sodium conditions (P ≤0.05 for all). Dietary sodium-by-mental stress interactions were significant for mean NN, RMSSD, high-frequency power, LFnu, and low frequency/high frequency ratio (P < 0.05 for all). The interactions signify that sodium restriction evoked an increase in resting sympathetic activity and reduced vagal activity to the extent that mental stress caused modest additional disruptions in autonomic balance. Conversely, normal and high sodium evoked a reduction in resting sympathetic activity and incremental increase in resting vagal activity, which were disrupted to a greater extent during mental stress compared to low sodium. CONCLUSION: We conclude that autonomic control of HRV at rest and during mental stress is altered by dietary sodium in healthy normotensive young adult men and women.