FJ. Heterogenous vasodilator pathways underlie flowmediated dilation in men and women. Am J Physiol Heart Circ Physiol 301: H1118 -H1126, 2011. First published June 3, 2011 doi:10.1152/ajpheart.00400.2011.-This study investigated the sex differences in the contribution of nitric oxide (NO) and prostaglandins (PGs) to flow-mediated dilation (FMD). Radial artery (RA) FMD, assessed as the dilatory response to 5-min distal cuff occlusion, was repeated after three separate brachial artery infusions of saline (SAL),, and ketorolac (KETO) ϩ L-NMMA in healthy younger men (M; n ϭ 8) and women (W; n ϭ 8).In eight subjects (4 M, 4W) RA FMD was reassessed on a separate day with drug order reversed (SAL, KETO, and L-NMMA ϩ KETO). RA FMD was calculated as the peak dilatory response observed relative to baseline (%FMD) and expressed relative to the corresponding area under the curve shear stress (%FMD/AUC SS). L-NMMA reduced %FMD similarly and modestly (P ϭ 0.68 for sex * trial interaction) in M and W (all subjects: 10.0 Ϯ 3.8 to 7.6 Ϯ 4.7%; P ϭ 0.03) with no further effect of KETO (P ϭ 0.68). However, all sex * trial and trial effects on %FMD/AUC SS for L-NMMA and KETO ϩ L-NMMA were insignificant (all P Ͼ 0.20). There was also substantial heterogeneity of the magnitude and direction of dilator responses to blockade. After L-NMMA infusion, subjects exhibited both reduced (n ϭ 14; range: 11 to 78% decrease) and augmented (n ϭ 2; range: 1 to 96% increase) %FMD. Following KETO ϩ L-NMMA, seven subjects exhibited reduced dilation (range: 10 to 115% decrease) and nine subjects exhibited augmented dilation (range: 1 to 212% increase). Reversing drug order did not change the nature of the findings. These findings suggest that RA FMD is not fully or uniformly NO dependent in either men or women, and that there is heterogeneity in the pathways underlying the conduit dilatory response to ischemia. shear stress; nitric oxide; prostaglandins; vasodilation BRACHIAL ARTERY FLOW-MEDIATED dilation (FMD), the shearevoked conduit artery dilatory response to a period of tissue ischemia, is a standard noninvasive technique for assessing endothelial function and has been correlated with coronary artery endothelial function (3). FMD is predictive of future cardiovascular events (21, 60), providing independent prognostic value to cardiovascular risk assessment in post menopausal women (48) and predicting future cardiac events in patients with established coronary artery disease (7).Reductions in FMD are widely assumed to reflect diminished nitric oxide (NO) dilator function as several pivotal human studies have concluded that brachial and radial artery FMD are dependent on a NO pathway (12,28,29,40). In these studies, blockade of NO by administration of the endothelial nitric oxide synthase (eNOS) inhibitor [N G -monomethyl-Larginine (L-NMMA)] in young, healthy humans abolished the conduit dilatory response to a 5-min period of distal occlusion. By contrast, a recent study (44) was unable to reduce radial FMD with a large dose of L-NMMA and conclude...

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Results suggest that the combination of air travel and marathon running induces an acute hypercoaguable state; this hemostatic imbalance is exaggerated with increasing age.

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The purpose of the study was to examine predictors of the leg hemodynamic response to exercise in middle- and older-aged men and women. Femoral artery blood flow (FBF), mean arterial pressure (MAP), and femoral vascular conductance (FVC, calculated as the quotient of FBF and MAP) were measured at rest and during 5 min of single knee-extensor exercise at ~10 W workload in healthy men (n = 31) and women (n = 32) (age 40-72 years). Age, menopausal status, maximal quadriceps strength, blood lipids, vitamin D levels, maximal oxygen uptake (VO(2max)), physical activity, blood pressure, estimated quadriceps muscle mass, and body mass index (BMI) were also assessed. The effect of age on FBF and FVC was negative and significant in men (r = -0.44 and -0.42 and p = 0.01 and 0.02, respectively) but was abolished by normalization to estimated quadriceps muscle (p = 0.18 and 0.73, respectively). There was no effect of age on leg hemodynamic responses to exercise in women (alone or normalized to quadriceps muscle), but menopausal status was a significant predictor of FVC and normalized FVC (p = 0.04 and 0.02, respectively). The multivariate model for exercising FVC in men (in order of strongest to weakest predictors) included quadriceps strength, BMI, resting FVC, age, and high-density lipoprotein cholesterol. The multivariate model for exercising FVC in women included quadriceps mass, systolic blood pressure, vitamin D, age, VO(2max), waist circumference, and physical activity score. These findings suggest that factors besides chronological age mediate exercising leg hemodynamics in middle-aged to older adults and that these factors are sex-specific.

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