Inhibition of brain acetylcholine biosynthesis by methyldopa in spontaneously hypertensive rats.
The formation of 3H-acetylcholine was measured in several brain regions of spontaneously hypertensive (SH) rats following intracerebroventricular injection of 3H-choline. Endogenous acetylcholine (ACh) also was measured and specific activity-time curves for brain ACh generated for control SH rats and for SH rats pretreated with methyldopa (100-200 mg/kg, IV). The relative turnover rates for ACh in several brain regions was estimated from the specific activity-time curves. The turnover rates of ACh in rostral hypothalamus, caudal hypothalamus, medulla oblongata and pons were reduced by 34-54%. Apparently synthesis was inhibited also since methyldopa produced relatively little effect on ACh levels. More rostral brain regions, thalamus-septum, midbrain and striatum, were not significantly affected by methyldopa. Methyldopa also reduced arterial pressure by 53/28 mmHg. The ability of methyldopa to inhibit the function of cholinergic neurons in selective brain regions may be responsible for its common "anticholinergic" side effects. Since centrally-acting anticholinergic drugs reduce arterial pressure in SH rats, it is possible that inhibition of brain ACh synthesis by methyldopa also may contribute to its antihypertensive action in experimental genetic hypertension.
D000109:Acetylcholine / Q000096:biosynthesis*; D000818:Animals; D002794:Choline / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D008636:Mesencephalon / Q000378:metabolism; D008750:Methyldopa / Q000494:pharmacology*; D011149:Pons / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D012688:Septum Pellucidum / Q000378:metabolism; D013788:Thalamus / Q000378:metabolism
D008750:Methyldopa; D002794:Choline; D000109:Acetylcholine