On the mechanism of central hypotensive action of clonidine.
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 less than 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 greater than 0.80) and GABA (p less than 0.70). Topical application of atropine (1%) also blocked (p less than 0.05) the hypotensive effect of clonidine. Intravenous administration of clonidine (50 microgram/kg) produced hypotension (34.6%) after an initial hypertensive response and bradycardia (38.8%). The hypotension was significantly (p less than 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 less than 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.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002415:Cats; D003000:Clonidine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005998:Glycine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D006426:Hemicholinium 3 / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects*; D010275:Parasympathetic Nervous System / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D006426:Hemicholinium 3; D005680:gamma-Aminobutyric Acid; D001285:Atropine; D003000:Clonidine; D000109:Acetylcholine; D005998:Glycine