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Inhibition of regional brain acetylcholine biosynthesis by clonidine in spontaneously hypertensive rats
Author(s) -
Buccafusco Jerry J.
Publication year - 1984
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430040605
Subject(s) - clonidine , acetylcholine , endocrinology , cholinergic , medicine , cholinergic neuron , pons , medulla oblongata , chemistry , central nervous system
Recent studies in this laboratory have demonstrated that clonidine, a centrally acting antihypertensive drug, can inhibit the function of central cholinergic neurons. We have also provided evidence for enhanced brain cholinergic activity in the spontaneously hypertensive rat (SHR). The purpose of this study was to determine whether the antihypertensive response to clonidine in the SHR could be correlated with a decrease in acetylcholine synthesis in several brain regions. Clonidine (30μg/kg, i.v.) produced a time‐dependent reduction in blood pressure (BP) in unrestrained SHR's of 18/16 and 27/22 mmHg by 10 min and 100 min, respectively. The formation of 3 H‐acetylcholine in the brain following pulse injection of 3 H‐choline (20 μCi) into the lateral cerebral ventricle was employed as an estimate of the rate of acetylcholine synthesis. Clonidine produced a time‐dependent inhibition of 3 H‐acetylcholine formation in several brain areas. For example, in the pons, 3 H‐acetylcholine formation was reduced by 21 and 44% at 10 min and 100 min following clonidine, respectively. Other brain regions to exhibit significant inhibition of cholinergic activity included the rostral and the caudal hypothalamus, medulla oblongata, thalamus‐septum, and midbrain. The striatum exhibited the greatest 3 H‐acetylcholine formation in control animals; however, this activity was not affected by clonidine. These results are consistent with the ability of clonidine, at a clinically relevant dose, to elicit concomitantly an antihypertensive response and a marked inhibition of brain cholinergic activity in SHRs. This finding in conjunction with the results from several previous studies suggest that central cholinergic neurons participate in mediating the antihypertensive action of clonidine.