Abstract 18950: Changes in Vasodilator Reactivity and Vasoconstrictor Tone in Metabolically Healthy Obesity and the Metabolic Syndrome

Abstract

Background: Patients with obesity-related metabolic syndrome (MetS) have endothelial dysfunction due to decrease nitric oxide (NO) availability and increased endothelin (ET)-1-mediated vasoconstrictor tone. Given the prognostic significance of endothelial dysfunction, these abnormalities may be involved in the increased risk of cardiovascular mortality of these patients. Whether patients with metabolically healthy obesity (MHO), in whom those metabolic abnormalities that define the MetS are not present, have similar impairment of endothelial function is unknown. Methods: Forearm blood flow (FBF) responses were measured by strain-gauge plethysmography during intra-arterial infusion of graded-doses of acetylcholine (ACh; an endothelial-dependent vasodilator) and sodium nitroprusside (SNP; an endothelium-independent vasodilator), and/or during selective antagonism of ETA receptors by BQ-123 (10 nmol/min for 60 minutes) in lean subjects (n=56) and in obese patients (n=119), with either MHO (n=34) or the MetS (n=85). Results: ACh and SNP caused vasodilation in both obese and lean participants (all P<0.001 vs. baseline). The response, however, 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 the MetS (P<0.001), whereas the responsiveness to SNP was equally impaired in both groups (P=0.45); this suggests higher degree of endothelial dysfunction in the MetS, but similar impairment of smooth muscle reactivity in MHO and the MetS. As expected, BQ-123 increased FBF in obese (P<0001 vs. baseline), but not in lean participants, hence the FBF response to ETA receptor blockade was higher in both obese groups than in controls (both P<0.001). In keeping with the ACh results, the FBF response to BQ-123 was significantly higher in patients with the MetS than in those with MHO (P=0.007). Conclusions: Patients with MHO have abnormal vascular reactivity, albeit their endothelial dysfunction is less pronounced than in patients with the MetS. These findings indicate that obesity per se is associated with some degree of vascular damage independently of those metabolic abnormalities underlying the MetS.