Prolonged supramaximal stimulation of canine efferent sympathetic neurons induces desensitization of inotropic responses without a change in myocardial beta-adrenergic receptors.
OBJECTIVE
To investigate whether desensitization of inotropic responses elicited during prolonged efferent sympathetic neural stimulation is due to decreased responsiveness of myocardial beta-adrenergic receptors or to alterations in the efferent sympathetic neurons innervating the heart.


METHODS
Increasing doses of noradrenaline and isoproterenol were administered intravenously before and during prolonged (20 mins) stimulation of the intrathoracic efferent sympathetic nervous system of eight dogs. Cardiac augmentor responses were correlated with liberation of catecholamines by the heart. In a second group of experiments (nine dogs), right and left ventricular beta-adrenergic receptor number and affinity were determined before and during such stimulations.


RESULTS
Similar ventricular augmentations were induced when isoproterenol or noradrenaline was administered before and after 20 mins of efferent sympathetic neural stimulation. During the early peak stimulation response, no further augmentations were induced by isoproterenol or noradrenaline. Liberation of noradrenaline by the heart followed a similar course after an initial peak, while noradrenaline values fell to levels which were 6% of those attained during peak response after 20 mins of continuous stimulation. The Bmax and Kd of ventricular beta-adrenergic receptors were similar before and after 20 mins of efferent sympathetic neural stimulation.


CONCLUSIONS
Desensitization of ventricular inotropism that occurs during prolonged cardiac efferent sympathetic nervous system stimulation is not primarily due to alteration of myocyte cell surface beta-adrenergic receptors or to a change in myocyte responsiveness to beta-adrenergic agonists, but rather to a reduction in noradrenaline release by sympathetic efferent post ganglionic neurons presumably reflecting a reduction in the activity of these neurons despite continued stimulation.
Watson-Wright
W M
WM
Department of Physiology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia.
Wilkinson
M
M
Johnstone
D E
DE
Cardinal
R
R
Armour
J A
JA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003864:Depression, Chemical; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006321:Heart / Q000294:innervation*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D009476:Neurons, Efferent / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol; D009638:Norepinephrine