Norepinephrine-induced phosphorylation of a 25 kd phosphoprotein in rat aorta is altered in intraperitoneal sepsis

An attenuation of the contractile response to norepinephrine (NE) has been previously demonstrated in rat aorta during intraperitoneal sepsis and endotoxemia. In this study, we determined whether NE-induced protein phosphorylation is altered in septic rat aorta as compared to control rat aorta. We found that the NE-induced phosphorylation of a 25 kd phosphoprotein was decreased. NE increased phosphorylation of the 25 kd band by 54% (P less than .01) in the control aorta but only 12% (not significant) in the septic aorta. Pyrophosphate gel purification of phosphorylated myosin showed that this 25 kd band was not related to the myosin-phosphorylated (P) light chain. Two-dimensional polyacrylamide gel electrophoresis analysis revealed that this 25 kd band represents two proteins with distinct isoelectric points of 6.5 and 6.2. These results further document that intrinsic alterations occur in the NE-mediated signal transduction system in rat aorta during sepsis and that such alterations could contribute to depressed aortic contractility.