Supersensitivity and changes in the active population of beta adrenoceptors in rat right atria in early sepsis.
We have investigated the effect of sepsis induced by cecal ligation and puncture on the chronotropic actions of beta adrenoceptor agonists on isolated right atria. The present findings show that right atria obtained from rats in an early stage of sepsis were supersensitive to the chronotropic actions of the beta-agonists, isoproterenol (ISO), fenoterol (FEN) and prenalterol (PREN). The supersensitivity to the chronotropic actions of ISO and FEN was much greater than that which developed to PREN. The positive chronotropic actions of isobutylmethylxanthine and forskolin were not affected by sepsis. The receptor subtypes mediating the responses to ISO, FEN and PREN by control and septic right atria were characterized by functional assays using selective beta-1 and beta-2 antagonists. The results showed that the chronotropic response produced by all three agonists on right atria obtained from control rats were mediated by beta-1 receptors. In contrast, the chronotropic actions of ISO and FEN on atria from septic rats were mediated by what appears to be beta-2 receptors and those of PREN by beta-1 receptors.
Department of Pharmacology, Louisiana State University Medical Center, New Orleans.
L A
LA
Barker
S L
SL
Winbery
L W
LW
Smith
K H
KH
McDonough
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D016275:Atrial Function; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000502:physiology*; D018805:Sepsis / Q000503:physiopathology*
D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; C026777:ICI 118551; D019204:GTP-Binding Proteins; D015056:1-Methyl-3-isobutylxanthine