title: Estrogen has opposing effects on vascular reactivity in obese, insulin-resistant male Zucker rats.
abstract: We hypothesized that estradiol treatment would improve vascular dysfunction commonly associated with obesity, hyperlipidemia, and insulin resistance. A sham operation or 17beta-estradiol pellet implantation was performed in male lean and obese Zucker rats. Maximal vasoconstriction (VC) to phenylephrine (PE) and potassium chloride was exaggerated in control obese rats compared with lean rats, but estradiol significantly attenuated VC in the obese rats. Estradiol reduced the PE EC50 in all groups. This effect was cyclooxygenase independent, because preincubation with indomethacin reduced VC response to PE similarly in a subset of control and estrogen-treated lean rats. Endothelium-independent vasodilation (VD) to sodium nitroprusside was similar among groups, but endothelium-dependent VD to ACh was significantly impaired in obese compared with lean rats. Estradiol improved VD in lean and obese rats by decreasing EC50 but impaired function by decreasing maximal VD. The shift in EC50 corresponded to an upregulation in nitric oxide synthase III protein expression in the aorta of the estrogen-treated obese rats. In summary, estrogen treatment improves vascular function in male insulin-resistant, obese rats, partially via an upregulation of nitric oxide synthase III protein expression. These effects are counteracted by adverse factors, such as hyperlipidemia and, potentially, a release of an endothelium-derived contractile agent.
authors.affiliation: Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Esther M
authors.initials: EM
authors.lastname: Brooks-Asplund
authors.forename: Artin A
authors.initials: AA
authors.lastname: Shoukas
authors.forename: Soon-Yul
authors.initials: SY
authors.lastname: Kim
authors.forename: Sean A
authors.initials: SA
authors.lastname: Burke
authors.forename: Dan E
authors.initials: DE
authors.lastname: Berkowitz
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D004435:Eating; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D066298:In Vitro Techniques; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D009765:Obesity / Q000503:physiopathology; D051381:Rats; D011924:Rats, Zucker; D013851:Thinness / Q000503:physiopathology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects* / Q000502:physiology
chemical_list: D004343:Drug Implants; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D004958:Estradiol; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat