Rosiglitazone restores nitric oxide synthase-dependent reactivity of cerebral arterioles in rats exposed to prenatal alcohol

Partha S. Saha, Kirsten R. Kim Sawtelle, Brittany N. Bamberg, Denise M. Arrick, Michael J. Watt, Jamie L. Scholl, Hong Zheng, William G. Mayhan

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: Prenatal exposure to alcohol leads to a greater incidence of many cardiovascular-related diseases, presumably via a mechanism that may involve increased oxidative stress. An agonist of peroxisome proliferator-activated receptor gamma (PPARγ; rosiglitazone) has been shown to suppress alcohol-induced neuroinflammation and oxidative stress. The goal of this study was to determine whether acute and chronic treatment with rosiglitazone could restore or prevent impaired nitric oxide synthase (NOS)-dependent responses of cerebral arterioles in male and female adult (14–16 weeks old) rats exposed to alcohol in utero. Methods: We fed Sprague-Dawley dams a liquid diet with or without 3% ethanol for the duration of their pregnancy (21–23 days). In the first series of studies, we examined the reactivity of cerebral arterioles to eNOS- (ADP), nNOS-dependent (NMDA), and NOS-independent agonists in male and female adult rats before and during acute (1 hour) topical application of rosiglitazone (1 µM). In a second series of studies, we examined the influence of chronic treatment with rosiglitazone (3 mg/kg/day in drinking water for 2–3 weeks) on the responses of cerebral arterioles in male and female adult rats exposed to alcohol in utero. Results: We found that in utero exposure to alcohol similarly reduced responses of cerebral arterioles to ADP and NMDA, but not to nitroglycerin in male and female adult rats. In addition, acute treatment of the male and female adult rats with rosiglitazone similarly restored this impairment in cerebral vascular function to that observed in controls. We also found that chronic treatment with rosiglitazone prevented impaired vascular function in male and female adult rats that were exposed to alcohol in utero. Conclusions: PPARγ activation may be an effective and relevant treatment to reverse or prevent cerebral vascular abnormalities associated with prenatal exposure to alcohol.

Original languageEnglish (US)
Pages (from-to)1359-1369
Number of pages11
JournalAlcoholism: Clinical and Experimental Research
Volume45
Issue number7
DOIs
StatePublished - Jul 2021

Keywords

  • cerebral vascular function
  • fetal alcohol syndrome
  • nitric oxide
  • oxidative stress
  • stroke

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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