On the mechanism of central hypotensive action of clonidine

Abstract

The hypotensive effect of clonidine in anaesthetised (pentobarbitone) cat has been analysed with the help of pharmacological tools. Application of clonidine (0.1%) to the exposed ventral surface of medulla oblongata produced hypotension (28.6%) and bradycardia (18%). Similar application of glycine (5%) and GABA (10%) also lowered the blood pressure of cat by 20.3% and 29.3%, respectively. The hypotension as well as the bradycardia owing to clonidine were significantly (p < 0.01) blocked by similar prior application of atropine methylnitrate (1%) and hemicholinium-3 (HC3, 1%). whereas HC3 pretreatment only insignificantly blocked the hypotension produced by glycine (p > 0.80) and GABA (p > 0.70). Topical application of atropine (1%) also blocked (p < 0.05) the hypotensive effect of clonidine.Intravenous administration of clonidine (50 μg/kg) produced hypotension (34.6%) after an intial hypertensive response and bradycardia (38.8%). The hypotension was significantly (p < 0.01) blocked by pretreatment of the cat with intracerebroventricular atropine (4 mg) or HC3 (0.5 mg). Topical application of atropine (1%) to the ventral surface of medulla also significantly (p < 0.05) reduced the hypotension and bradycardia resulting from intravenous administration of clonidine.It is concluded that an intact cholinergic link in the brainstem is essential for the hypotensive effect of clonidine.