Impaired endothelium-independent microvascular function in obese young adults
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Microvascular dysfunction is believed to precede the development and contribute to the progression of obesity related diseases such as insulin resistance, hypertension, and coronary artery disease. Multiple studies have found impaired microvascular endothelium-dependent vasodilation occurs prior to the onset of disease in middle aged adults. In order to test the hypothesis that the cutaneous microvasculature of young obese (BMI>30kg/m²), but otherwise healthy, adults would exhibit impaired microvascular response, we recruited 12 obese and 12 lean (BMI<25 kg/m²) individuals. Each group was age-matched and consisted of 5 females and 7 males. Each participant was instrumented with two microdialysis probes inserted in the dermis of the non-dominant forearm for a wide dose range of infusions of either the endothelium-dependent vasodilator methacholine (MCh) or the endothelium-independent vasodilator sodium nitroprusside (SNP). Each microdialysis site was clamped at 33°C with a local heater and affixed with a laser Doppler flux (LDF) probe for determination of local red blood cell flux, an index of blood flow. LDF was recorded continuously while 7 doses of each drug (MCh: 10⁻³-10³mM; SNP: 5x10⁻⁵-50mM) were infused at a rate of 2 [mu]l/min for 8 minutes per dose. Both sites finished with heating to 43°C and infusion of 50mM SNP to confirm site specific maximal vasodilation. Blood pressure was recorded in the last minute of each stage and the corresponding LDF was used to calculate cutaneous vascular conductance (CVC). Dose response curves for CVC at each dose, as well as maximal CVC were analyzed. MCh dose response showed a trend toward endothelium–dependent impairment in obese (p=0.06) and maximal absolute CVC at the MCh site was attenuated in obese versus lean (2.70 ± 0.73 vs 3.30 ± 0.81 LDF/mmHg, p=0.027). Endothelium-independent vasodilation with SNP was impaired at the 4 highest doses of SNP (all P<0.006) and maximal CVC was attenuated in obese compared to lean (2.44 ± 0.74 vs 3.31 ± 0.65 LDF/mmHg, p=0.004). These results support the hypothesis that microvascular function is impaired in young, healthy obese, individuals; however they suggest the impairment is partially endothelium-independent.