title: Vasodilator responses and endothelin-dependent vasoconstriction in metabolically healthy obesity and the metabolic syndrome.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Catholic University Medical School, Rome, Italy;
authors.forename: Francesca
authors.initials: F
authors.lastname: Schinzari
authors.affiliation: Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland; Department of Medicine, Cardiology Division, Johns Hopkins Hospital, Baltimore, Maryland;
authors.forename: Micaela
authors.initials: M
authors.lastname: Iantorno
authors.affiliation: MedStar Cardiovascular Research Network, Washington, DC;
authors.forename: Umberto
authors.identifier: http://orcid.org/0000-0002-7894-3565
authors.initials: U
authors.lastname: Campia
authors.affiliation: Department of Pharmacology, Catholic University Medical School, Rome, Italy; and.
authors.forename: Nadia
authors.initials: N
authors.lastname: Mores
authors.affiliation: Department of Internal Medicine, University of Tor Vergata, Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Rovella
authors.affiliation: Department of Internal Medicine, University of Tor Vergata, Rome, Italy.
authors.forename: Manfredi
authors.initials: M
authors.lastname: Tesauro
authors.affiliation: Department of Internal Medicine, University of Tor Vergata, Rome, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Di Daniele
authors.affiliation: Department of Internal Medicine, Catholic University Medical School, Rome, Italy; carmine.cardillo@rm.unicatt.it.
authors.forename: Carmine
authors.identifier: http://orcid.org/0000-0001-5182-3005
authors.initials: C
authors.lastname: Cardillo
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D019332:Endothelin-1 / Q000378:metabolism / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000503:physiopathology*; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D000067329:Obesity, Metabolically Benign / Q000503:physiopathology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D019332:Endothelin-1; D010456:Peptides, Cyclic; D009599:Nitroprusside; D000109:Acetylcholine; C072247:cyclo(Trp-Asp-Pro-Val-Leu)
keywords: endothelin-1; endothelium; metabolic syndrome; obesity; vasodilation