Minimal modification of canine ventricular myocyte cell surface beta adrenoceptors despite desensitisation of ventricular function during exogenous beta adrenoceptor challenge.
OBJECTIVE
The aim was to determine whether a 120 min exposure of ventricular myocytes to beta agonist challenge alters ventricular cell surface beta adrenergic receptors concomitant with desensitisation of ventricular function.


METHODS
Supramaximal doses of isoprenaline (1 microgram.kg-1.min-1 intravenously) were given continuously to anaesthetised dogs for 15 (n = 6), 60 (n = 2), and 120 (n = 6) min. Changes induced during beta adrenoceptor challenge in right and left ventricular systolic pressures were correlated with right and left ventricular myocyte beta adrenoceptor number and affinity.


RESULTS
Isoprenaline initiated early augmentation in right [23(SEM 3)-78(10) mm Hg] and left [82(6)-186(11) mm Hg] ventricular intramyocardial systolic pressures. After 5 min of continuous exogenous beta agonist challenge these pressures were reduced to 42(4) mm Hg and 104(16) mm Hg, respectively, even though the agonist challenge persisted. Throughout the subsequent 115 min exposure period these pressures remained relatively similar. Despite these inotropic effects the number (Bmax) and affinity (Kd) of ventricular myocyte beta adrenergic cell surface receptors, as determined by the tissue slice technique, were similar before and after 15, 60, and 120 min exposure to isoprenaline.


CONCLUSIONS
(1) After the desensitisation of the initial enhancement of ventricular inotropism that occurs during the first 5 min of a beta agonist challenge, inotropism remains relatively constant for the next 115 min exposure. (2) Desensitisation of ventricular inotropism elicited during 2 h exposure of the in situ heart to a beta agonist challenge is not primarily due to altered myocyte cell surface beta adrenergic receptor number or affinity.
Watson-Wright
W M
WM
Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
Wilkinson
M
M
Cardinal
R
R
Boudreau
G
G
Armour
J A
JA
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004285:Dogs; D004837:Epinephrine / Q000097:blood; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D013268:Stimulation, Chemical; D013997:Time Factors
D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol; C033394:CGP 12177; D009638:Norepinephrine; D004837:Epinephrine