5 g) or high (2 g) basal tension for short (1 hour) or long duration (24 hours). Isometric contraction in response to phenylephrine (Phe, 10(-5) mol/L), angiotensin II (AngII, 10(-6)

mol/L), and KCl was measured. The veins were frozen to determine the expression and localization of MMPs using immunoblots and immunohistochemistry.\n\nResults. In IVC segments subjected to 0.5 g tension for 1 hour, Phe and AngII produced significant contraction. At higher 2 g basal tension for Selleckchem Givinostat 24 hours, both Phe and AngII contractions were significantly reduced. Reduction in KCl contraction was also observed at high 2 g basal tension for 24 hours, suggesting that the reduction in vein contraction is not specific to a particular receptor, and likely involves inhibition of a post-receptor contraction mechanism. In vein segments under 2 g tension for 24 hours and treated with TIMP-1, Phe, AngII, and KCl contractions were partially restored, suggesting the involvement of MMps. IVC immunoblot analysis demonstrated

prominent bands corresponding to MMP-2 and MMP-9 protein. High 2 g wall tension for 24 hours was associated with marked increase in the amount of MMP-2 and -9 relative check details to the housekeeping protein actin. There was a correlation between MMP expression and decreased vein contraction. Also, significant increases in MMP-2 and -9 immunostaining were observed in IVC segments subjected to high 2 g tension for 24 hours. click here Both MMP-2 and MMP-9 caused significant inhibition of Phe contraction in IVC segments.\n\nConclusions: In rat IVC, increases in magnitude and duration of wall tension is associated with reduced contraction and overexpression of MMP-2 and -9. In light of our findings that MMP-2 and -9 promote IVC relaxation,

the data suggest that protracted increases in venous pressure and wall tension increase MMPs expression, which in turn reduce venous contraction and lead to progressive venous dilation.”
“The activities of promoters can be temporally and conditionally regulated by mechanisms other than classical DNA-binding repressors and activators. One example is the inherently weak Sigma(70)-dependent Pr promoter that ultimately controls catabolism of phenolic compounds. The activity of Pr is up-regulated through the joint action of ppGpp and DksA that enhance the performance of RNA polymerase at this promoter. Here, we report a mutagenesis analysis that revealed substantial differences between Pr and other ppGpp/DksA co-stimulated promoters. In vitro transcription and RNA polymerase binding assays show that it is the T at the -11 position of the extremely suboptimal -10 element of Pr that underlies both poor binding of Sigma(70)-RNAP and a slow rate of open complex formation-the process that is accelerated by ppGpp and DksA. Our findings support the idea that collaborative action of ppGpp and DksA lowers the rate-limiting transition energy required for conversion between intermediates on the road to open complex formation.