Inhibitory effects of pregnancy on insulin relaxant effects in thoracic and abdominal rat aorta

抄録

Insulin can inhibit vascular smooth muscle contraction but vasodilation is impaired in hypertensive hyperinsulinemic patients. Besides, hyperinsulinemia and insulin resistance are metabolic physiological features of pregnancy that are not associated with hypertension in normal conditions. To understand the effect of pregnancy on the vascular effects of insulin, we sought to compare insulin (0.1-1.2 mU/mL) induced relaxation of isolated thoracic or abdominal rat aorta rings with and without endothelium precontracted with phenylephrine. Our goal was to see whether pregnancy effect was different depending on the vascular segment and if it is dependent on nitric oxide or prostaglandins. Insulin induced vasodilation was unchanged by removal of endothelium. Pregnancy (days 14 and 20) significantly attenuated the relaxant effect of low concentrations of insulin (0.1-0.3 mU/mL) in the thoracic aorta, and of high insulin concentrations (0.6-1,2 mU/mL) in the abdominal aorta . Also, the addition of L-NAME 10-6M or indomethacin 10-6M inhibit vasodilation produced by high concentrations of insulin from thoracic but not from the abdominal aorta form pregnant rats at term. These results suggest increased insulin levels pregnancy is associated with resistance to the vasodilator effects of the peptide. Pregnancy effect seems to be endothelium independent, to differ depending on the aortic segment and is evident from mid pregnancy to term. Both NOS and COX contribute to insulin sensitivity at the end of pregnancy in the thoracic aorta.