Augmented dilation to nitric oxide in uterine arteries from rats with type 2 diabetes: Implications for vascular adaptations to pregnancy

Styliani Goulopoulou, Johanna L. Hannan, Takayuki Matsumoto, Adviye Ergul, R Clinton Webb

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Pre-existing diabetes increases the risk of maternal and fetal complications during pregnancy, which may be due to underlying maternal vascular dysfunction and impaired blood supply to the uteroplacental unit. Endothelial dysfunction and reduced vascular smooth muscle responsiveness to nitric oxide (NO) are common vascular impairments in type 2 diabetes (T2D). We hypothesized that uterine arteries from diabetic rats would have reduced vascular smooth muscle sensitivity to NO compared with nondiabetic rats due to impairment in the NO/soluble guanylate cyclase (sGC)/cGMP signaling pathway. Uterine arteries from pregnant Goto-Kakizaki (GK; model of T2D) and Wistar (nondiabetic) rats were studied in a wire myograph. GK nonpregnant uterine arteries had reduced responses to ACh and sodium nitroprusside (SNP) but increased responses to propylamine propylamine NONOate and greater sensitivity to sildenafil compared with Wistar nonpregnant arteries. In late pregnancy, Wistar rats had reduced uterine vascular smooth muscle responsiveness to SNP, but GK rats failed to show this adaptation and had reduced expression of sGC compared with the nonpregnant state. GK rats had a smaller litter size (13.9 ± 0.48 vs. 9.8 ± 0.75; P < 0.05) and a greater number of resorptions compared with Wistar controls (0.8 ± 0.76% vs. 19.9 ± 6.06%; P < 0.05). These results suggest that uterine arteries from rats with T2D show reduced sensitivity of uterine vascular smooth muscle sGC to NO. During pregnancy, the GK uterine vascular smooth muscle fails to show relaxation responses similar to those of arteries from nondiabetic rats.

Original languageEnglish (US)
Pages (from-to)H610-H618
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume306
Issue number4
DOIs
StatePublished - Feb 15 2014

Keywords

  • Gestation
  • Soluble guanylate cyclase
  • Uterine artery
  • Vascular smooth muscle
  • Vasorelaxation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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