Endothelial function is thought to be an important factor in the pathogenesis of atherosclerosis, hypertension and heart failure. In the 1990s, high-frequency ultrasonographic imaging of the brachial artery to assess endothelium-dependent flow-mediated vasodilation (FMD) was developed. The technique provokes the release of nitric oxide, resulting in vasodilation that can be quantitated as an index of vasomotor function. The noninvasive nature of the technique allows repeated measurements over time to study the effectiveness of various interventions that may affect vascular health. However, despite its widespread use, there are technical and interpretive limitations of this technique. State-of-the-art information is presented and insights are provided into the strengths and limitations of high-resolution ultrasonography of the brachial artery to evaluate vasomotor function, with guidelines for its research application in the study of endothelial physiology.

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Abstract-Diets rich in fruits and vegetables reduce blood pressure (BP) and the risk of adverse cardiovascular events.However, the mechanisms of this effect have not been elucidated. Certain vegetables possess a high nitrate content, and we hypothesized that this might represent a source of vasoprotective nitric oxide via bioactivation. In healthy volunteers, approximately 3 hours after ingestion of a dietary nitrate load (beetroot juice 500 mL), BP was substantially reduced (⌬ max Ϫ10.4/8 mm Hg); an effect that correlated with peak increases in plasma nitrite concentration. The dietary nitrate load also prevented endothelial dysfunction induced by an acute ischemic insult in the human forearm and significantly attenuated ex vivo platelet aggregation in response to collagen and ADP. Interruption of the enterosalivary conversion of nitrate to nitrite (facilitated by bacterial anaerobes situated on the surface of the tongue) prevented the rise in plasma nitrite, blocked the decrease in BP, and abolished the inhibitory effects on platelet aggregation, confirming that these vasoprotective effects were attributable to the activity of nitrite converted from the ingested nitrate. These findings suggest that dietary nitrate underlies the beneficial effects of a vegetable-rich diet and highlights the potential of a "natural" low cost approach for the treatment of cardiovascular disease. Key Words: diet Ⅲ nitric oxide Ⅲ blood pressure Ⅲ hypertension Ⅲ ischemia/reperfusion Ⅲ platelets Ⅲ endothelium P erhaps the largest public health initiative in the Western world has focused on improvement of diet, particularly in those with a high risk of cardiovascular disease. Trials have shown that diets rich in fruits and vegetables reduce blood pressure (BP; Dietary Approaches to Stop Hypertension; DASH, Vegetarian Diet and BP) 1,2 and adverse cardiovascular events. [3][4][5][6][7] These protective effects have previously been attributed to the high antioxidant vitamin content, yet large clinical trials have failed to provide evidence in support of this thesis. 8,9 The greatest protection against coronary heart disease afforded by a change in diet is that associated with the consumption of green leafy vegetables (eg, spinach, lettuce). 6 Such vegetables, also including beetroot, commonly have a high inorganic nitrate (NO 3 Ϫ ) content. 10,11 In humans, after absorption through the stomach wall, Ϸ25% of consumed nitrate enters the enterosalivary circulation where it is reduced to nitrite (NO 2 Ϫ ) by bacterial nitrate reductases from facultative anaerobes on the dorsal surface of the tongue. [12][13][14] This nitrite is swallowed and in the acidic environment of the stomach is reduced to nitric oxide (NO) or re-enters the circulation as nitrite. Indeed, it has been hypothesized that dietary nitrate represents an intravascular source of the pleiotropic, vasoprotective molecule NO, which supplements conventional NO generation by NO synthases (NOS). 15 Endothelium-derived NO is a potent dilator, governs systemic BP, and retards atheroge...

Congenital heart disease (CHD) is the leading cause of mortality from birth defects. Exome sequencing of a single cohort of 2,871 CHD probands including 2,645 parent-offspring trios implicated rare inherited mutations in 1.8%, including a recessive founder mutation in GDF1 accounting for ~5% of severe CHD in Ashkenazim, recessive genotypes in MYH6 accounting for ~11% of Shone complex, and dominant FLT4 mutations accounting for 2.3% of Tetralogy of Fallot. De novo mutations (DNMs) accounted for 8% of cases, including ~3% of isolated CHD patients and ~28% with both neurodevelopmental and extra-cardiac congenital anomalies. Seven genes surpassed thresholds for genome-wide significance and 12 genes not previously implicated in CHD had > 70% probability of being disease-related; DNMs in ~440 genes are inferred to contribute to CHD. There was striking overlap between genes with damaging DNMs in probands with CHD and autism.