title: NO-dependent endothelial dysfunction in type II diabetes is aggravated by dyslipidemia and hypertension, but can be restored by angiotensin-converting enzyme inhibition and weight loss.
abstract: OBJECTIVE
  Insulin resistance, dyslipidemia and hypertension are independent mediators of endothelial dysfunction. It is incompletely defined whether dyslipidemia and hypertension in addition to diabetes mellitus type II (DMII), as seen in the metabolic syndrome (MS), worsen diabetes-induced endothelial dysfunction. Furthermore, it is unclear whether treatment influences endothelial dysfunction similarly in MS and DMII. Therefore, we studied vascular reactivity and the effect of in vivo treatment with angiotensin-converting enzyme inhibition (ACE-I) or hypocaloric diet in LDL receptor- and leptin-deficient (ob/ob), double knockout mice (DKO), featuring MS and in ob/ob mice with DMII.
  
  
  RESULTS
  Vascular reactivity was studied in isolated aortic ring segments. Maximum vasorelaxant response to acetylcholine (Ach) was more depressed in DKO than in ob/ob mice, whereas response to bradykinin (BK) was equally attenuated in both genotypes (52 ± 3 and 23 ± 9% reversal of preconstriction induced by 10(-7) M phenylephrine in DKO vs. 76 ± 3 and 23 ± 8% reversal of preconstriction in ob/ob mice, respectively). ACE-I and hypocaloric diet improved ACh-induced vasorelaxation significantly (89 ± 2 and 59 ± 2% reversal of preconstriction in DKO vs. 80 ± 3 and 84 ± 4% in ob/ob mice, respectively), but not the response to BK.
  
  
  CONCLUSIONS
  These results indicate a differential impact of DMII and MS on endothelial function. ACE-I and hypocaloric diet improved ACh-, but not BK-induced vasorelaxation in these mouse models of DMII and MS.
authors.affiliation: Department of Cardiovascular Sciences, Research Unit of Experimental Cardiac Surgery, KU Leuven, Leuven, Belgium.
authors.forename: Ines
authors.initials: I
authors.lastname: Nevelsteen
authors.forename: An
authors.initials: A
authors.lastname: Van den Bergh
authors.forename: Gerry
authors.initials: G
authors.lastname: Van der Mieren
authors.forename: Annelies
authors.initials: A
authors.lastname: Vanderper
authors.forename: Kanigula
authors.initials: K
authors.lastname: Mubagwa
authors.forename: Hidde
authors.initials: H
authors.lastname: Bult
authors.forename: Paul
authors.initials: P
authors.lastname: Herijgers
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D031204:Caloric Restriction; D002216:Captopril / Q000494:pharmacology*; D003131:Combined Modality Therapy; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D050171:Dyslipidemias / Q000097:blood / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006973:Hypertension / Q000097:blood / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D020738:Leptin / Q000172:deficiency / Q000235:genetics; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D009569:Nitric Oxide / Q000378:metabolism*; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D015431:Weight Loss
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D001786:Blood Glucose; D020738:Leptin; D008055:Lipids; D011973:Receptors, LDL; D014665:Vasodilator Agents; D009569:Nitric Oxide; D002216:Captopril