Alterations in bidirectional transmembrane calcium flux occur without changes in protein kinase C levels in rat aorta during sepsis.
A depression in aortic contractility has been previously demonstrated in rat intraperitoneal sepsis and during endotoxemia. In this study, we determined whether the mobilization of extracellular calcium (using 45Ca) and the release of intracellular calcium are altered in septic rat aorta when compared to sham-operated controls. The concentration of protein kinase C was also determined by using [3H] phorbol-12,13-dibutyrate (PDBu). We found that calcium influx was unaltered under basal conditions but that the ability of norepinephrine (NE) to augment influx was significantly depressed (P less than .05; [control vs. septic, 572 +/- 54 [SE] vs. 428 +/- 30 mumol Ca2+/kg dry wt. aorta]). Calcium influx stimulated by high K+ was unchanged in aortae between control and septic animals. In the presence of NE, calcium efflux (an indirect measurement of intracellular calcium release) was significantly diminished (P less than .001) in aortae from septic rats. The concentration of aortic protein kinase C as assessed by PDBu binding sites was unaltered in septic rats when compared with controls. In conclusion, we found that during sepsis alpha 1-adrenergic receptor activation of both calcium influx and efflux by NE is decreased; these alterations could be related to the depressed aortic contractility observed in sepsis.
Litten
R Z
RZ
Physiology Department, Naval Medical Research Institute, Bethesda, Maryland 20814-5145.
Carcillo
J A
JA
Roth
B L
BL
D000818:Animals; D001011:Aorta / Q000032:analysis / Q000378:metabolism*; D001665:Binding Sites / Q000187:drug effects; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D018805:Sepsis / Q000378:metabolism*; D013997:Time Factors
D010703:Phorbol Esters; D011942:Receptors, Adrenergic, alpha; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D002118:Calcium; D009638:Norepinephrine