Fetal Hypothyroidism Impairs Aortic Vasorelaxation Responses in Adulthood: Involvement of Hydrogen Sulfide and Nitric Oxide Cross talk

Abstract

Thyroid hormones have a wide range of effects on growth, differentiation, evolution, metabolism, and physiological function of all tissues, including the vascular bed. In this study, the effect of fetal hypothyroidism on impairment of aortic vasorelaxation responses in adulthood was investigated with emphasis on possible involvement of hydrogen sulfide (H2S)/nitric oxide interaction. Two groups of female rats were selected. After mating and observation of vaginal plaque, one group received propylthiouracil (200 ppm in drinking water) until the end of pregnancy and another group had no propylthiouracil treatment during the fetal period. In adult rats, aortic relaxation responses to l-arginine and GYY4137 were assessed in the presence or absence of Nω-nitro-L-arginine methyl ester hydrochloride and dl-propargylglycine in addition to the biochemical measurement of thyroid hormones and some related factors. Obtained findings showed a lower vasorelaxation response for GYY4137 and l-arginine in the fetal hypothyroidism group, and preincubation with Nω-nitro-L-arginine methyl ester hydrochloride or dl-propargylglycine did not significantly aggravate this weakened relaxation response. In addition, aortic levels of sirtuin 3, endothelial nitric oxide synthase, cystathionine gamma-lyase, and H2S were significantly lower in the fetal hypothyroidism group. Meanwhile, no significant changes were obtained regarding serum levels of thyroid hormones including free triiodothyronine;, total triiodothyronine, free thyroxine, total thyroxine, and thyroid-stimulating hormone in adult rats. It can be concluded that hypothyroidism in the fetal period has inappropriate effects on the differentiation and development of vascular bed with subsequent functional abnormality that persists into adulthood, and part of this vascular abnormality is mediated through weakened interaction and/or cross talk between H2S and nitric oxide.