More recently, Hanssen et al.  found that exercise training-induced increases in arteriolar caliber were accompanied by significant decreases in ADMA, suggesting that the NO/ADMA pathway EPZ-6438 clinical trial may play a key role in the beneficial changes
in microvascular structure associated with regular exercise. The effect of obesity on the retinal microcirculation has been well established. Arteriolar caliber narrowing, venular caliber widening and lower AVR have been found to be associated with obesity in both children and adult populations [18,27,28,57,59,60], suggesting that obesity may cause deleterious microvascular changes before clinical signs and symptoms of vascular disease are present. In children, greater BMI was associated with wider retinal venular caliber and narrower arterioles, weight and body surface area were associated with wider retinal venules only, and larger waist circumference was associated with narrower retinal arterioles . In the SCORM , greater BMI and weight were associated check details with wider retinal venular caliber. Consistent with this evidence, more recent studies also demonstrated that BMI and triceps skinfold [14,37] were found to be associated with wider retinal venular caliber and narrower retinal
arteriolar caliber in healthy, pre-adolescent children, supporting an early adverse effect of obesity on microvascular crotamiton structure. Although the mechanisms underlying the association between obesity and retinal vessel diameter are unclear, several possible explanations exist. Systemic inflammation is thought to contribute to the vascular complications
associated with obesity . Systemic inflammation is also associated with changes in retinal venular caliber , and therefore may be the mechanism through which obesity affects retinal microvascular structure. Obesity is also related to increased total blood volume , and retinal venular dilatation may be a regulatory response to maintain blood flow. These relationships between obesity and retinal microvascular changes may help explain the association between childhood obesity and complications such as hypertension, diabetes, and cardiovascular morbidity and mortality that occur later in life . The Rotterdam Study , BDES , MESA , Wisconsin Epidemiologic Study of Diabetic Retinopathy , and BMES  have all demonstrated a consistent association between wider retinal vessel caliber and cigarette smoking, suggesting that adverse macrovascular outcomes associated with smoking may be partly mediated by deleterious changes in microvascular health. More recently, the ARIC study has demonstrated a temporal association between past smoking and wider retinal venules, independent of current smoking status , indicating that smoking may provoke long-term structural changes in microcirculation.