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Increased Expression of mRNA for RGS containing RhoGEFs in Aorta from Stroke Prone Spontaneously Hypertensive Rats

, : Increased Expression of mRNA for RGS containing RhoGEFs in Aorta from Stroke Prone Spontaneously Hypertensive Rats. FASEB Journal 18(4-5): Abst 818 13

The RhoA/Rho-kinase signaling pathway regulates vascular tone and is implicated in the pathophysiology of hypertension. The activation of RhoA by Rho guanine exchange factors (RhoGEFs) links the RhoA/Rho-kinase pathway to G protein coupled receptor (GPCR). Since the RGS domain is responsible for the interaction with heterometeric G proteins, the group of RhoGEFs containg the RGS domain (p115RhoGEF, leukemia-associated Rho guanine nucleotide exchange factor (LARG) and PDZ-RhoGEF(, are most likely to directly link the GPCR to Rho/Rho-kinase pathway. To test the hypothesis that RhoGEFs is responsible for the increased activation of RhoA/Rho-kinase pathway in hypertension, a semi-quantitative RT-PCR based assay of the RGS domain containing RhoGEFs mRNA was established and used to examine the RGS containing RhoGEFs mRNA in aorta from rats with normotension or spontaneous hypertension. Of the three RGS containing RhoGEFs, p115RhoGEF is the only one with a commercially available antibody, thus western blot and the established semi-quantitative RT-PCR was performed on the same samples. The consistence of the results from these two different methods ensured the reliability of the established semi-quantitative RT-PCR assay. The examination showed that compared to WKY normotensive rats, the mRNA expression of RGS domain containing RhoGEFs is up-regulated in SHRSP. This observation provides a possible explanation for increased vascular reactivity in hypertension via GPCR coupling to RhoA/Rho-kinase signaling.


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