Peer-Reviewed Journal Details
Mandatory Fields
Hogan, K,Ahmed, O,Markos, F;
Autonomic Neuroscience-Basic & Clinical
N-desmethylclozapine an M1 receptor agonist enhances nitric oxide's cardiac vagal facilitation in the isolated innervated rat right atrium
Optional Fields
muscarinic receptors neuronal nitric oxide vagus heart N-desmethylclozapine MUSCARINIC RECEPTORS HEART CLOZAPINE UNIQUE NNOS PIG
We have previously determined that neuronal nitric oxide (NO) may partly mediate its established cholinergic effect via activation of muscarinic type 1 (MI) receptors located at the preganglionic/postganglionic synapse. In this series of experiments we set out to confirm this finding using an M I agonist. Experiments were carried out on the isolated vagally innervated right atrium in the presence of atenolol (4 mu M). The right vagus was stimulated at 4, 8, 16, 32 Hz; pulse duration 1 ms at 20 V for 20 s and the effect on cardiac interval (ms) assessed. N-desmethylelozapine (100 nM), a potent MI agonist, enhanced the vagally induced increase in cardiac interval, a lower concentration of 50 nM had no significant effect on cardiac interval. This effect was prevented by pre-treatment of the atria with the neuronal NO synthase inhibitor 1 (2-trifluoromethylphenyl)imidazole (TRIM) at 0.14 mM. The vagal stimulation protocol was repeated in order to rule out a reduction in vagal effectiveness which may have been due to the experimental stimulation protocol used in this study. TRIM (0.14 mM) alone causes a small but significant attenuation of the vagally induced increase in cardiac interval. These results show that agonism of MI receptors on cardiac vagal preganglionic fibres enhances vagal cardiac effects which can be prevented by a neuronal NO inhibitor. (c) 2007 Elsevier B.V. All rights reserved.
DOI 10.1016/j.autneu.2007.07.002
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