Alterations in Bidirectional Transmembrane Calcium Flux Occur Without Changes in Protein Kinase C Levels in Rat Aorta during Sepsis

摘要

Human sepsis and septic shock are frequent causes of death in clinical medicine. Septic shock is characterized by peripheral vasodilation with a decreased systemic vascular resistance and hypotension. In an attempt to increase the vascular resistance and elevate blood pressure, clinicians usually administer catecholamines and catecholamine derivatives. However, a diminished peripheral vascular responsiveness to catecholamines is commonly observed, thus making this approach frequently ineffective. In this study we determined whether calcium mobilization was altered in aortae from septic rats during the stimulation of alpha 1 -adrenergic receptors by NE. Calcium influx through calcium channels and calcium efflux, an indication of intracellular calcium release by the sarcoplasmic reticulum, were measured in the rat aortae. Both processes in rat aorta are stimulated by the activation of alpha 1 - adrenoceptors. In addition, we measured the levels of protein kinase C as determined by PDBu binding sites in aortae from septic light chain as well as alter calcium influx in vascular smooth muscle and induce rat aortic contraction. We have also shown that activation of protein kinase C inhibits PI hydrolysis, which could explain, in part, the diminished PI turnover observed in the rat aorta during sepsis. Reprints. (kt)