Study On The Effect Of Vasoconstriction Alteration And RAS Regulatory Mechanism In Middle Cerebral Artery In Rat Offspring By Prenatal Hypoxia

Objectives: To determine the influence on angiotensin II-mediated vasoconstriction and the underlying mechanism in middle cerebral arteries(MCA) of adult offspring by prenatal hypoxia.Methods: Pregnant rats were randomly divided into two groups(control group, hypoxia group), 10 rats in each group. Rats in hypoxia group were provided with 10.5% oxygen concentration in hypoxic box from the gestation day 5 to day 21, the control group rats into normoxic box. Offspring rats grew up to 5 months in normoxic environment,take the male for experiments. Changes in the contractile responses induced by Ang II in middle cerebral artery of hypoxia group were detected through DMT vascular tension detection system. By the combined use of non-selective inhibitor of PKC receptor GF109203 X, ERK signaling pathway inhibitor U0126 or ROK signaling pathway inhibitor Y27632, to further explore the relationship between changes in the contractile responses induced by Ang II and PKC and key points of its downstream signal pathway. In addition, to detect the m RNA levels of RAS, PKC pathway related protein in offspring MCA in two groups by RT-PCR method.Results: The contractile responses to angiotensin II were stronger in the hypoxia MCA than that of the control. AT1 receptors, not AT2 receptors mediated the increased vasoconstrictions. GF109203 X, a PKC antagonist, suppressed the angiotensin II-increased vasoconstriction, while PKC agonist phorbol12.13-dibutyrate(PDBu) produced greater contractile responses in MCA by prenatal hypoxia than that of the control. ROK antagonist Y-27632 suppressed the PDBu-increased vasoconstriction. However, in the presence of ERK inhibitor(U0126), the PDBu induced contractions were increased. The m RNA levels of PKCα was increased, while PKCδ unchanged. The m RNA levels of ROKβ was increased, while ERK2 reduced.Conclusions: The data suggest that hypoxia in pregnancy enhanced angiotensin II-mediated vasoconstriction in the offspring MCA, which could be partially attributed to increased expression of AT1 receptors,PKCα, and changes in PKC/ERK,ROK pathway regulation.