An intracerebroventricular perfusion system developed for the study of centrally acting antihypertensive drugs in the rat.
A method for the complete construction and employment of an intracerebroventricular perfusion system for the rat brain is described. Rats maintained on the system for up to 7 hr displayed no detectable change in cardiovascular status. Penetration of intracerebroventricular-administered methylene blue dye into all areas of the cerebroventricles demonstrated the accessibility of the injection volume throughout the ventricular system. The hypotensive and bradycardic response produced by a 1.5-microgram/kg dose of clonidine (a centrally active antihypertensive agent) administered via the intracerebroventricular implant was of considerably greater magnitude and duration than an equivalent intravenous dose. Administration of [3H]-labeled clonidine via the intracerebroventricular implant resulted in relatively minor accumulation of the drug into peripheral organs, when compared to that found in the brain. These supportive data suggest the general applicability of this approach for studying the selective central effects of pharmacologic agents in a relatively inexpensive and easily procured laboratory animal.
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002408:Catheters, Indwelling; D002552:Cerebral Ventricles; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation; D004867:Equipment Design; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D010477:Perfusion / Q000295:instrumentation* / Q000379:methods; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains
D000959:Antihypertensive Agents; D003000:Clonidine