Study of the participation of eNOS phosphorylated on serine 1177 and threonine 495 in the hiporeactivity of the aortas to phenylephrine observed in pregnant Wistar and SHR.

Abstract

Normotensive and spontaneously hypertensive rats (SHR) show a significant decrease in blood pressure during the last period of pregnancy which is associated with vascular hiporeactivity to some vasoconstrictor agonists. These effects have been attributed to a higher modulation of nitric oxide (NO) and to an increased activity of nitric oxide synthase (NOS) eNOS. PI3-K/Akt phosphorylates eNOS on serine and threonine. The basal phosphorylated NOSe expression is increased in aorta from pregnant rats. However, the role of the phosphorylated NOSe on the aorta reactivity to phenylephrine was not determined in pregnancy. The aim of this study is evaluate the participation of eNOS phosphorylated on serine 1177 and threonine 495 in the hiporeactivity of the aortas to phenylephrine observed in pregnant Wistar and SHR. We will evaluate the effects of wortmannin (PI3K/AKT inhibitor) on the vasoconstriction of the aortas from pregnant rats that will be stimulated by phenylephrine, Ach and SNP. Our hypothesis is that wortmannin should reverse the aorta hiporeactivity to Phe, but not change the reactivity to Ach and SNP. Subsequently, aortas are processed to evaluate the expression (Western blot) of NOS phosphorylated on serine 1177 and threonine 495. Our hypothesis is that the contraction of aortas from pregnant rats to Phe increases the phosphorylation of eNOS on serine residues, but does not alter the phosphorylation on threonine. Some differences should be observed between the aortas of pregnant normotensive and hypertensive rats (SHR). Keywords: pregnancy, eNOS, vascular reactivity, serine 1177, threonine 495, wortmannin.