Myocardial beta adrenergic receptor coupling to adenylate cyclase during developing septic shock.
The present review is focused on one potential mechanism that may contribute to cardiac failure during developing septic shock. Evidence that sympathetic stimulation is intense in response to septic insult is presented and is related to possible desensitization of adrenergic mechanisms that mobilize cardiac reserve. Disruption of this signal transduction mechanism may be critical in that viable working myocardium becomes reduced as part of the tissue injury process during septic insult, thus requiring increased performance of remaining myocardial tissue. Evidence in support of adrenergic desensitization in the heart during sepsis is presented and is related to current concepts developed from cell-systems. Experiments examining a septic insult and evidence for down regulation of beta-adrenergic receptors, possible uncoupling of beta-receptors to adenylate cyclase, characteristics of beta-receptor agonist binding, and possible internalization of surface receptors are reviewed and discussed. In general, results suggest that changes in the heart occur during sepsis that are typical of adrenergic desensitization. The limited amount of experimental evidence supporting these interpretations and areas of needed research are highlighted.
Jones
S B
SB
Department of Physiology, Loyola University Medical Center, Maywood, Illinois 60153.
Romano
F D
FD
D000262:Adenylyl Cyclases / Q000502:physiology*; D000818:Animals; D002415:Cats; D004285:Dogs; D015536:Down-Regulation / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012772:Shock, Septic / Q000503:physiopathology*
D011943:Receptors, Adrenergic, beta; D000262:Adenylyl Cyclases; D009638:Norepinephrine; D004837:Epinephrine