Ventricular, but not atrial, M2-muscarinic receptors increase in the canine pacing-overdrive model of heart failure.
OBJECTIVE
To investigate the effects of heart failure induced by chronic rapid ventricular pacing (six weeks) on canine atrial and ventricular muscarinic receptors.


METHODS
Dogs (n = 4) were fitted with a bipolar pacing electrode connected to a Medtronic pacemaker set at 240 stimuli/min. Pacing was maintained for six weeks. Tissue samples obtained from the left atrium and ventral wall of the left ventricle were frozen at -70 degrees C. Control tissue was obtained from normal dogs (n = 6) following anesthesia and thoracotomy. M2-muscarinic receptors were characterized and quantified in tissue micropunches using the hydrophilic ligand [3H] N-methyl-scopolamine (NMS).


RESULTS
Cardiac tissue bound [3H] NMS with the specificity of an M2 subtype. Tachycardia-induced heart failure did not affect atrial muscarinic receptors but signify left ventricular myocytes (control 160.0 +/- 10.0 fmol/mg protein versus heart failure 245.0 +/- 25.0 fmol/mg protein; P < 0.01).


CONCLUSIONS
Canine ventricular muscarinic receptors display a specificity for the M2 subtype. In contrast to previous work, tachycardia-induced heart failure was accompanied by an increase (+ 53%) in ventricular, but not atrial, M2 receptors compared with normal dogs.
Wilkinson
M
M
Department of Obstetrics and Gynaecology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia.
Giles
A
A
Armour
J A
JA
Cardinal
R
R
D000818:Animals; D001665:Binding Sites; D002304:Cardiac Pacing, Artificial / Q000009:adverse effects*; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006325:Heart Atria / Q000473:pathology; D006333:Heart Failure / Q000209:etiology / Q000473:pathology*; D006352:Heart Ventricles / Q000473:pathology*; D008297:Male; D019832:N-Methylscopolamine; D011976:Receptors, Muscarinic / Q000032:analysis*; D012602:Scopolamine Derivatives
D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D019832:N-Methylscopolamine