bay-63-2521 and Non-alcoholic-Fatty-Liver-Disease

Fibrotic processes in the liver of non-alcoholic steatohepatitis (NASH) patients cause microcirculatory dysfunction in the organ which increases blood vessel resistance and causes portal hypertension. Assessing blood vessel function in the liver is challenging, necessitating the development of novel methods in normal and fibrotic tissue that allow for drug screening and translation toward pre-clinical settings. Cultures of precision cut liver slices (PCLS) from normal and fibrotic rat livers were used for blood vessel function analysis. Live recording of vessel diameter was used to assess the response to endothelin-1, serotonin and soluble guanylate cyclase (sGC) activation. A cascade of contraction and relaxation events in response to serotonin, endothelin-1, Ketanserin and sGC activity could be established using vessel diameter analysis of rat PCLS. Both the sGC activator BI 703704 and the sGC stimulator Riociguat prevented serotonin-induced contraction in PCLS from naive rats. By contrast, PCLS cultures from the rat CCl

Topics: Adenosine Triphosphate; Animals; Blood Vessels; Carbon Tetrachloride; Endothelin-1; Ketanserin; Liver; Liver Cirrhosis; Male; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Pyrazoles; Pyrimidines; Rats, Sprague-Dawley; Rats, Wistar; Serotonin; Signal Transduction; Soluble Guanylyl Cyclase; Vasoconstriction; Vasodilation