Central muscarinic involvement in cardiovascular control in sinoaortic-denervated rats.
A study was made of the cardiovascular effects of centrally administered cholinergic drugs in conscious sham-operated or sinoaortic-denervated (SAD) rats. Neostigmine (0.01-1 micrograms) and bethanechol (0.125-2 micrograms), injected intracerebroventricularly (i.c.v.), induced a dose-dependent increase in mean blood pressure. This effect was significantly greater in SAD rats than in sham-operated rats. The heart rate was reduced by both neostigmine and bethanechol in sham-operated rats but remained unaltered in SAD animals. Similar doses of neostigmine and bethanechol injected i.v. did not have an effect in sham-operated rats. Central muscarinic blockade with methylatropine (1 or 5 micrograms i.c.v.) prevented the cardiovascular effects induced by neostigmine (1 microgram i.c.v.) in both groups of rats. The administration of methylatropine (0.3 mg/kg i.v.) to sham-operated rats only prevented the bradycardia induced by neostigmine (1 microgram i.c.v.), the pressor response was not affected. These results lend support to the view that cholinergic pathways are involved in the pressor and bradycardic responses of sham-operated rats and that they are mediated through central muscarinic receptors. The bradycardia induced by lower doses of the anticholinesterase, neostigmine, cannot be reflex-mediated. The fact that the pressor response to neostigmine was higher in SAD rats than in sham-operated animals could be either due to a different activity of the cholinergic pathways or to an abolition of baroreflex afferent activity. These results also suggest that there is a connection between central cholinergic pathways and baroreflex efferent activity.
Taira
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CA
Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, UBA, Argentina.
Enero
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MA
D000818:Animals; D001286:Atropine Derivatives / Q000494:pharmacology; D001626:Bethanechol Compounds / Q000008:administration & dosage / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D003714:Denervation; D006339:Heart Rate / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D009388:Neostigmine / Q000008:administration & dosage / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D012849:Sinoatrial Node / Q000502:physiology*
D001286:Atropine Derivatives; D001626:Bethanechol Compounds; D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D009388:Neostigmine; C006649:methylatropine