Inhibition of regional brain acetylcholine biosynthesis by clonidine in spontaneously hypertensive rats

✍ Scribed by Dr. Jerry J. Buccafusco

• Publisher: John Wiley and Sons
• Year: 1984
• Tongue: English
• Weight: 477 KB
• Volume: 4
• Category: Article
• ISSN: 0272-4391
• DOI: 10.1002/ddr.430040605

✦ Synopsis

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 (30pg/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 3H-acetylcholine in the brain following pulse injection of 3H-choline (20 pCi) into the lateral cerebral ventricle was employed as an estimate of the rate of acetylcholine synthesis. Clonidine produced a time-dependent inhibition of 3H-acetylcholine formation in several brain areas. For example, in the pons, 3H-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 rostra1 and the caudal hypothalamus, medulla oblongata, thalamusseptum, and midbrain. The striatum exhibited the greatest 3H-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.