Changes in muscarinic cholinergic-beta adrenergic interactions in isolated rat papillary muscle after 6-hydroxydopamine pretreatment: evidence for compensatory muscarinic supersensitivity.
The purpose of this study was to examine whether adaptive changes occur in beta adrenergic-muscarinic cholinergic interactions in the control of cardiac contractility after chronic interruption of the sympathetic input. Attenuation of the contractile response to beta adrenoceptor stimulation by muscarinic agonists was studied in isolated left ventricular papillary muscles from control rats and rats pretreated with 6-hydroxydopamine (6-OHDA) hydrobromide (2 X 50 mg/kg i.v. at 24-h intervals) and killed 3 days to 3 weeks later. Pretreatment with 6-OHDA increased the inotropic sensitivity to isoproterenol, expressed as a left shift of the concentration-response curve, at 3 days, 1 week, and 2 weeks. However, the inotropic concentration-response curve for isoproterenol was not significantly shifted at 3 weeks. In control tissues, a maximally effective concentration of carbachol produced a 3.8-fold shift of the isoproterenol concentration-response curve to the right. This carbachol-induced right shift was increased to 9.8-, 7.9-, 9.5- and 4.6-fold at 3 days and 1, 2 and 3 weeks, respectively, after 6-OHDA treatment. Additional experiments were performed to examine the concentration-response for muscarinic agonists in attenuating the inotropic response to a maximally effective concentration of isoproterenol. The potency of carbachol was increased 1.8-fold (3 days), 2.7-fold (1 week), 2.8-fold (2 weeks) and 2.3-fold (3 weeks) after 6-OHDA pretreatment. A 2.0-fold increase in the potency of oxotremorine was also observed at 2 weeks. In addition, the maximal effect of both agonists was increased in tissues from 6-OHDA-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Chen
W Y
WY
Department of Zoological and Biomedical Sciences, Ohio University, Athens.
Wince
L C
LC
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D006892:Hydroxydopamines / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine; D010095:Oxotremorine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*
D006892:Hydroxydopamines; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D010095:Oxotremorine; D016627:Oxidopamine; D002217:Carbachol; D007545:Isoproterenol; D009638:Norepinephrine