Vasodilator responses and endothelin-dependent vasoconstriction in metabolically healthy obesity and the metabolic syndrome.

Patients with metabolically healthy obesity (MHO) do not present the cluster of metabolic abnormalities that define the metabolic syndrome (MetS). Whether MHO is associated with lower impairment of vasoreactivity than the MetS is unknown. For this purpose, forearm blood flow (FBF) responses were measured by strain-gauge plethysmography during the intra-arterial infusion of acetylcholine (ACh), sodium nitroprusside (SNP), and/or the selective endothelin type A (ETA) receptor blocker BQ-123 in 119 obese individuals with MHO (n = 34) or with the MetS (n = 85) and in healthy lean controls (n = 56). ACh and SNP caused a significant vasodilation in both obese and lean participants (all P < 0.001). However, the response to both agents was significantly lower in the obese than in the control group (both P < 0.001). Among the obese participants, the reactivity to ACh was higher in MHO than in MetS patients, whereas the responsiveness to SNP was equally impaired in both groups (P = 0.45). Infusion of BQ-123 significantly increased FBF in obese patients (P < 0001), but not in the lean participants; hence, FBF following ETA receptor blockade was higher in both obese groups than in controls (both P < 0.001). FBF response to BQ-123 was significantly higher in patients with the MetS than in those with MHO (P = 0.007). In conclusion, patients with MHO have abnormal vascular reactivity, although their endothelial dysfunction is less pronounced than in patients with the MetS. These findings indicate that obesity is associated with vascular damage independent of those metabolic abnormalities underlying the MetS.