Estrogen has opposing effects on vascular reactivity in obese, insulin-resistant male Zucker rats

Esther M. Brooks-Asplund, Artin A. Shoukas, Soon Yul Kim, Sean A. Burke, Dan E Berkowitz

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


We hypothesized that estradiol treatment would improve vascular dysfunction commonly associated with obesity, hyperlipidemia, and insulin resistance. A sham operation or 17β-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.

Original languageEnglish (US)
Pages (from-to)2035-2044
Number of pages10
JournalJournal of applied physiology
Issue number5
StatePublished - 2002


  • Cyclooxygenase
  • Hormones
  • Indomethacin
  • Nitric oxide synthase
  • Non-insulin-dependent diabetes mellitus

ASJC Scopus subject areas

  • Medicine(all)


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