Mechanisms Underlying Chronic Binge Alcohol Exposure-Induced Uterine Artery Dysfunction in Pregnant Rat

Overview

Journal Alcohol Clin Exp Res

Specialty Psychiatry

Date 2018 Jan 25

PMID 29363778

Citations 11

Authors

Vishal D Naik

Katie Davis-Anderson

Kaviarasan Subramanian

Raine Lunde-Young

Matthew J Nemec

Jayanth Ramadoss

Affiliations

Soon will be listed here.

Abstract

Background: A cardinal feature of fetal alcohol syndrome is growth restriction. Maternal uterine artery adaptations to pregnancy correlate with birthweight and survival. We hypothesized that gestational binge alcohol exposure impairs maternal uterine vascular function, affecting endothelial nitric oxide (NO)-mediated vasodilation.

Methods: Pregnant rats grouped as pair-fed control or binge alcohol exposed received a once-daily, orogastric gavage of isocaloric maltose-dextrin or alcohol, respectively. On gestational day 20, primary uterine arteries were isolated, cannulated, and connected to a pressure transducer, and functional studies were conducted by dual-chamber arteriography. Uterine arteries maintained at constant intramural pressure (90 mm Hg) were maximally constricted with thromboxane, and a dose-response for acetylcholine (Ach) was recorded.

Results: The alcohol group exhibited significantly impaired endothelium-dependent, Ach-induced uterine artery relaxation (↓∼30%). Subsequently, a dose-response was recorded following inhibition of endothelium-derived hyperpolarizing factor (apamin and TRAM-34) and prostacyclin (indomethacin). Ach-induced relaxation in the pair-fed control decreased by ~46%, and interestingly, relaxation in alcohol group further decreased by an additional ~48%, demonstrating that gestational binge alcohol impairs the NO system in the primary uterine artery. An endothelium-independent sodium nitroprusside effect was not observed. Immunoblotting indicated that alcohol decreased the level of endothelial excitatory P-Ser endothelial NO synthase (eNOS) (p < 0.05) and total eNOS expression (p < 0.05) compared to both the normal and pair-fed controls. P-Ser eNOS level was also confirmed by immunofluorescence imaging.

Conclusions: This is the first study to demonstrate maternal binge alcohol consumption during pregnancy disrupts uterine artery vascular function via impairment of the eNOS vasodilatory system.

Citing Articles

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References

Luksha L, Agewall S, Kublickiene K . Endothelium-derived hyperpolarizing factor in vascular physiology and cardiovascular disease. Atherosclerosis. 2008; 202(2):330-44. DOI: 10.1016/j.atherosclerosis.2008.06.008. View

Mount P, Kemp B, Power D . Regulation of endothelial and myocardial NO synthesis by multi-site eNOS phosphorylation. J Mol Cell Cardiol. 2006; 42(2):271-9. DOI: 10.1016/j.yjmcc.2006.05.023. View

Thomas J, Sather T, Whinery L . Voluntary exercise influences behavioral development in rats exposed to alcohol during the neonatal brain growth spurt. Behav Neurosci. 2008; 122(6):1264-73. PMC: 3164868. DOI: 10.1037/a0013271. View

Sokol R, Delaney-Black V, Nordstrom B . Fetal alcohol spectrum disorder. JAMA. 2003; 290(22):2996-9. DOI: 10.1001/jama.290.22.2996. View

May P, Gossage J, Kalberg W, Robinson L, Buckley D, Manning M . Prevalence and epidemiologic characteristics of FASD from various research methods with an emphasis on recent in-school studies. Dev Disabil Res Rev. 2009; 15(3):176-92. DOI: 10.1002/ddrr.68. View

Riley E, McGee C . Fetal alcohol spectrum disorders: an overview with emphasis on changes in brain and behavior. Exp Biol Med (Maywood). 2005; 230(6):357-65. DOI: 10.1177/15353702-0323006-03. View

Musicki B, Kramer M, Becker R, Burnett A . Inactivation of phosphorylated endothelial nitric oxide synthase (Ser-1177) by O-GlcNAc in diabetes-associated erectile dysfunction. Proc Natl Acad Sci U S A. 2005; 102(33):11870-5. PMC: 1187969. DOI: 10.1073/pnas.0502488102. View

Hipolito U, Callera G, Simplicio J, De Martinis B, Touyz R, Tirapelli C . Vitamin C prevents the endothelial dysfunction induced by acute ethanol intake. Life Sci. 2015; 141:99-107. DOI: 10.1016/j.lfs.2015.09.006. View

Conrad K, Joffe G, Kruszyna H, Kruszyna R, Rochelle L, Smith R . Identification of increased nitric oxide biosynthesis during pregnancy in rats. FASEB J. 1993; 7(6):566-71. View

10.

Halpern W, Osol G, Coy G . Mechanical behavior of pressurized in vitro prearteriolar vessels determined with a video system. Ann Biomed Eng. 1984; 12(5):463-79. DOI: 10.1007/BF02363917. View

11.

Popova S, Stade B, Bekmuradov D, Lange S, Rehm J . What do we know about the economic impact of fetal alcohol spectrum disorder? A systematic literature review. Alcohol Alcohol. 2011; 46(4):490-7. DOI: 10.1093/alcalc/agr029. View

12.

Sun H, Mayhan W . Sex difference in nitric oxide synthase-dependent dilatation of cerebral arterioles during long-term alcohol consumption. Alcohol Clin Exp Res. 2005; 29(3):430-6. DOI: 10.1097/01.alc.0000156117.87892.22. View

13.

Cudd T, Chen W, West J . Fetal and maternal thyroid hormone responses to ethanol exposure during the third trimester equivalent of gestation in sheep. Alcohol Clin Exp Res. 2002; 26(1):53-8. View

14.

Sahna E, Kurcer Z, Ozturk F, Cengiz N, Vardi N, Birincioglu M . Effects of chronic ethanol consumption on alpha-adrenergic-induced contractions and endothelium-dependent relaxations in rat thoracic aorta. Pharmacol Res. 2000; 41(6):629-33. DOI: 10.1006/phrs.1999.0629. View

15.

Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R, Zeiher A . Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature. 1999; 399(6736):601-5. DOI: 10.1038/21224. View

16.

Tufan A, Lale Satiroglu-Tufan N . The effect of ethanol exposure on extraembryonic vascular development in the chick area vasculosa. Cells Tissues Organs. 2003; 175(2):84-97. DOI: 10.1159/000073752. View

17.

Falconer J . The effect of maternal ethanol infusion on placental blood flow and fetal glucose metabolism in sheep. Alcohol Alcohol. 1990; 25(4):413-6. View

18.

Kenny L, Baker P, Kendall D, Randall M, Dunn W . Differential mechanisms of endothelium-dependent vasodilator responses in human myometrial small arteries in normal pregnancy and pre-eclampsia. Clin Sci (Lond). 2002; 103(1):67-73. DOI: 10.1042/cs1030067. View

19.

Thomas J, Idrus N, Monk B, Dominguez H . Prenatal choline supplementation mitigates behavioral alterations associated with prenatal alcohol exposure in rats. Birth Defects Res A Clin Mol Teratol. 2010; 88(10):827-37. PMC: 3677823. DOI: 10.1002/bdra.20713. View

20.

Chinnathambi V, Balakrishnan M, Ramadoss J, Yallampalli C, Sathishkumar K . Testosterone alters maternal vascular adaptations: role of the endothelial NO system. Hypertension. 2013; 61(3):647-54. PMC: 3596870. DOI: 10.1161/HYPERTENSIONAHA.111.00486. View