Unexpected hyperactivity of myocardial adenylate cyclase system in endotoxic male rats.
Ventricle beta-adrenoceptors have been investigated and serum steroid levels determined in male rats injected intravenously with lipopolysaccharide from E. coli (LPS) under light anesthesia. Two series of doses were successively studied: 1) 2 and 3 mg.kg-1 and 2) 1 and 4 mg.kg-1, each including controls. The second series was carried out owing to the unexpected results of the first one. Homogeneity of the two series was tested. Experiments were performed at hr 4 after injection, a time previously tested to induce hormonal variations and release of a cardiodepressant factor (CDF) in serum. The results indicate that 2 mg.kg-1 LPS induced an increased activity of adenylate cyclase. The unexpectedly high response was dose-dependent since it was not found with the lowest or highest doses. The determination of serum steroid levels (progesterone, 17 alpha-hydroxyprogesterone, corticosterone, delta 4-androstenedione, testosterone, estrone, and estradiol) was used as a kind of marker of endotoxin activity. The results point out that the light anesthesia used for LPS injection delayed the hormonal response, when compared with results previously obtained with the same LPS dose (2 mg.kg-1) in unanesthetized rats. It can be inferred that the present data should usually appear at an earlier stage. It is suggested that an endotoxin-induced protein kinase C activation could be involved in the observed hyperactivity of adenylate cyclase and the hyperdynamic phase of septic shock.
Laboratoire de Pharmacologie Biochimique, CHU Cochin-Port-Royal, Paris, France.
C
C
Gardey
G
G
Thiroux
N
N
Christeff
A
A
Carli
D019326:17-alpha-Hydroxyprogesterone; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000735:Androstenedione / Q000097:blood; D000818:Animals; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006908:Hydroxyprogesterones / Q000097:blood; D007700:Kinetics; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D011374:Progesterone / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000139:chemically induced / Q000201:enzymology*; D013739:Testosterone / Q000097:blood
D006908:Hydroxyprogesterones; D008070:Lipopolysaccharides; D013739:Testosterone; D000735:Androstenedione; D011374:Progesterone; D019326:17-alpha-Hydroxyprogesterone; D006160:Guanosine Triphosphate; D000262:Adenylyl Cyclases; D003345:Corticosterone