Abstract
1. The present studies evaluated the participation of central muscarinic receptors in the cardiovascular effects of centrally injected neostigmine, a quaternary anticholinesterase, in conscious, sham-operated rats and in sinoaortic denervated animals. 2. The dose-dependent pressor effect of neostigmine (0.1 to 1 μg ICV) was greater in sinoaortic denervated rats than in sham-operated animals, but only a dose-dependent bradycardic effect was seen in sham-operated rats. 3. Doses of 3.3 nmol (ICV) of both the M 1 muscarinic antagonist, pirenzepine, and the M 3 muscarinic antagonist, 4-DAMP, prevented the pressor response to 1 μg of neostigmine in sham-operated rats and in sinoaortic denervated animals; however, the M 2 muscarinic antagonist, AF-DX116, partially blocked this response in sham-operated rats while failing to do so in sinoaortic denervated rats. In sham rats, doses of 3.3 nmol (ICV) of both pirenzepine and 4-DAMP prevented the bradycardic response to 1 μg (ICV) of neostigmine, whereas AF-DX116 induced a partial blockade. 4. 4-DAMP, at the dose of 0.3 nmol (ICV), but not pirenzepine at the same dose, prevented the pressor effect of neostigmine (0.1 to 1 μg ICV) in both groups of rats. Both muscarinic antagonists at this dose prevented the bradycardia elicited by the anticholinesterase (0.1 to 1 μg ICV), but 4-DAMP showed a greater antagonistic action on this cardiac effect than pirenzepine. In sham-operated rats, ICV injection of 0.3 nmol of AF-DX116 failed to modify the cardiovascular responses to 0.3 μg of neostigmine. 5. Results suggest mainly an involvement of brain M 3-subtype muscarinic receptors in the cardiovascular effect of intracerebroventricular administration of anticholinesterase neostigmine in both groups of rats.
Published Version
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