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

作者：Goulopoulou Styliani^*; Hannan Johanna L; Matsumoto Takayuki; Ergul Adviye; Webb R Clinton

来源：American Journal of Physiology - Heart and Circulatory Physiology, 2014, 306(4): H610-H618.

DOI：10.1152/ajpheart.00588.2013

• uterine artery
• soluble guanylate cyclase
• vascular smooth muscle
• vasorelaxation
• gestation

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.

• 出版日期2014-2
• 单位河北医科大学