Kost, Susan L.

Dietary sodium loading decreases β‐adrenergic receptor mediated vasodilation in hypertensive men, and paradoxically increases this dilation in normotensive men; no information exists in women. The purpose of this investigation was to test the hypothesis that dietary sodium loading and restriction influences β‐receptor mediated vasodilation in a sex‐dependent manner. Healthy normotensive subjects consumed a high (400 mmol/day, n=36, mean age±SEM 23±1 yr, 23 women) or low (10 mmol/day, n=30, 30±1 yr, 14 women) sodium diet for 5 days prior to study. Forearm blood flow (FBF, plethysmography) responses to brachial artery administration of isoproterenol (ISO: 1, 3, 6, 12 ng/100 ml tissue/min) were measured before and after endothelial NO synthase inhibition with N G ‐monomethyl‐L‐arginine (L‐NMMA). Consistent with prior reports, the FBF response to ISO was greater in men on high sodium compared to men on low sodium (p=0.03, ISO‐by‐sodium interaction). The highest response to ISO was 16.6±1.7 and 11.0±1.1 ml/100 ml tissue/min (high vs. low, p=0.01). After LNMMA the men's response to ISO did not differ based on sodium. In contrast, in women dietary sodium did not affect the response to ISO before or after LNMMA. We conclude that dietary sodium alters β‐adrenergic receptor mediated vasodilation in men, which appears to be dependent on NO. This is the first study to suggest that these mechanisms of vasodilation are resistant to dietary sodium in women. Support: HL‐089331, CTSA RR‐024150

Dietary sodium influences intermediate physiological traits in healthy young adults independent of changes in blood pressure. The purpose of this study was to test the hypothesis that dietary sodium affects cardiac autonomic function. In prospective, randomized cross‐over design separated by 1 month or more between diets, 69 normotensive healthy young adults (M/F: 26/43, ages 18–38 yr) consumed a 5‐day low (10 mmol/day), normal (150 mmol), and high sodium (400mmol) diet prior to a protocol examining cardiovascular traits including heart rate variability (HRV) by time domain and frequency domain analysis (Nevrokard). All women were studied in the low hormone phase of the menstrual cycle. Diet did not affect blood pressure, but HR (mean ± SE) was 68±1, 65±1, and 64±1 in low, normal, and high sodium conditions, resp. (RM ANOVA p < 0.01). For HRV there was a main effect of sodium on SDNN, RMSSD, HF, LFnu, HFnu, and LF/HF ratio (p < 0.01 for all). The response to low sodium was most marked and consistent with sympathetic activation, with increased LFnu and LF/HF ratio, and decreased SDNN, RMSSD, and HFnu compared to both normal and high sodium conditions (p ≤ 0.05 for all). These findings suggest that autonomic control of HRV is altered through changes in dietary sodium without changes in blood pressure. Support: UL1 TR000135 , HL‐89331

AimA 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.MethodWe 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−1forearm 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 endothelialNOsynthase inhibition with intra‐arterialNG‐monomethyl‐l arginine acetate (L‐NMMA).ResultsAgeing was associated with a significantly reducedFVCresponse toACh(P= 0.009, age‐by‐dose interaction; highest doseFVC±SEMin ageing: 11.2 ± 1.4vs.younger: 17.7 ± 2.4 units,P= 0.02). Celecoxib did not reduce restingFVCor the responses toAChin any group.L‐NMMAsignificantly reduced restingFVCand the responses toAChin all groups, and absoluteFVCvalues followingL‐NMMAwere similar between groups.ConclusionIn healthy normotensive younger and older adults, there is minimal contribution of prostacyclin toACh‐mediated vasodilation, yet theNOcomponent 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 ofCOX‐2 medications reduces endothelium dependent vasodilation in older persons with or without cardiovascular risk factors.

Dietary sodium and blood pressure regulation differs between normotensive men and women, an effect which may involve endothelial production of nitric oxide (NO). Therefore, we tested the hypothesis that differences in the NO component of endothelium-dependent vasodilation between low and high dietary sodium intake depend on sex. For 5 days prior to study, healthy adults consumed a controlled low-sodium diet (10 mmol/day, n = 30, mean age ± SE: 30 ± 1 yr, 16 men) or high-sodium diet (400 mmol/day, n = 36, age 23 ± 1 yr, 13 men). Forearm blood flow (FBF, plethysmography) responses to brachial artery administration of acetylcholine (ACh, 4 μg·100 ml tissue−1·min−1) were measured before and after endothelial NO synthase inhibition with NG-monomethyl-l-arginine (l-NMMA, 50 mg bolus + 1 mg/min infusion). The NO component of endothelium-dependent dilation was calculated as the response to ACh before and after l-NMMA accounting for changes in baseline FBF: [(FBF ACh − FBF baseline) − (FBF AChL-NMMA − FBF baselineL-NMMA)]. This value was 5.7 ± 1.3 and 2.5 ± 0.8 ml·100 ml forearm tissue−1·min−1 for the low- and high-sodium diets, respectively (main effect of sodium, P = 0.019). The sodium effect was larger for the men, with values of 7.9 ± 2.0 and 2.2 ± 1.4 for men vs. 3.1 ± 1.3 and 2.7 ± 1.0 ml·100 ml forearm tissue−1·min−1 for the women ( P = 0.034, sex-by-sodium interaction). We conclude that the NO component of endothelium-dependent vasodilation is altered by dietary sodium intake based on sex, suggesting that endothelial NO production is sensitive to dietary sodium in healthy young men but not women.