Peripherally and centrally mediated bradycardiac effects of clonidine in anesthetized or spinal rats.
The bradycardia-inducing  effects of clonidine were examined in anesthetized or spinal rats by injecting the drug intracisternally (i.c.) or intravenously (i.v.). Clonidine (1-25mug i.c.) caused a bradycardia dose-dependently in anesthetized rats. The bradycardia in response to clonidine (5mug i.c.) was significantly reduced after a treatment with phentolamine (100 mug i.c.), but not influenced with atropine (1 mg i.v.) or sectioning bilateral cervical vagal nerves. In spinal rats, an acceleration in heart rate by electrical stimulation of cervical sympathetic nerves was frequency-dependent and that due to desmethylimipramine (DMI) was dose-dependent. Clonidine (30 mug i.v.) significantly inhibited the acceleration induced by electrical stimulations only at a low frequency (0.3-3 Hz) or DMI (0.3 mg i.v.). This inhibition by clonidine was antagonized by phentolamine (5 mg i.v.). Clonidine (30 mug i.v.) did not significantly influence the acceleration in heart rate of spinal rats induced by norepinephrine (1 mug i.v.), tyramine (100 mug i.v.) or 1,1-dimethyl-4-phenylpiperazinium (DMPP, 50 mug i.v.). Therefore, it is suggested that clonidine causes a bradycardia by stimulating both peripheral and central alpha-adrenoceptors, the sympathetic trunk is the main pathway, and that the peripheral mechanism for clonidine-induced bradycardia is different from the action of guanethidine or hexamethonium on a release of catecholamines from the cardiac nerve terminals.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000009:adverse effects*; D003891:Desipramine / Q000494:pharmacology; D004558:Electric Stimulation; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology; D051381:Rats; D013564:Sympathetic Nervous System / Q000187:drug effects; D013565:Sympatholytics / Q000494:pharmacology; D013566:Sympathomimetics / Q000494:pharmacology
D010276:Parasympatholytics; D013565:Sympatholytics; D013566:Sympathomimetics; D003000:Clonidine; D003891:Desipramine