ABSTRACT
The cholinergic marker vesicular acetylcholine transporter (VAChT) was investigated in different cerebral areas of spontaneously hypertensive rats (SHR) by immunochemistry (Western blot analysis) and by immunohistochemistry. SHR were used as an animal model of hypertensive brain damage. The sensitivity of manipulation of cholinergic system on VAChT was assessed in rats treated for four weeks with the acetylcholinesterase (AChE) inhibitor galantamine (3 mg/Kg/day). VAChT concentrations were increased in the brain of control SHR compared to age-matched normotensive Wistar-Kyoto rats. This increase probably represents an up-regulation of VAChT to oppose cholinergic deficits reported in SHR and is countered by galantamine administration. The possibility that cholinergic neurotransmission enhancement may represent a therapeutic strategy in cerebrovascular disease is discussed.
Subject(s)
Brain/metabolism , Cholinesterase Inhibitors/therapeutic use , Hypertension/drug therapy , Hypertension/metabolism , Vesicular Acetylcholine Transport Proteins/metabolism , Animals , Biomarkers/metabolism , Blood Pressure/drug effects , Brain/physiopathology , Cerebellum/metabolism , Cerebral Cortex/metabolism , Cholinergic Fibers/drug effects , Cholinesterase Inhibitors/pharmacology , Disease Models, Animal , Dose-Response Relationship, Drug , Galantamine/pharmacology , Hippocampus/metabolism , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Synaptic Transmission/drug effectsABSTRACT
The expression and microanatomical localization of the muscarinic cholinergic m5 receptor subtype was investigated in rat circle of Willis and pial arteries by in situ hybridization, immunoblotting and immunohistochemistry. In situ hybridization histochemistry revealed a strong signal in the endothelium of circle of Willis and pial arteries and a moderate signal in the tunica media of the same arteries, within smooth muscle. Exposure of membranes of arteries to anti-m5 receptor protein antibodies caused the development of a band of approximately 81 kDa. Immunohistochemistry revealed the accumulation of m5 receptor protein immunoreactivity primarily within endothelium of circle of Willis and cerebral arteries and to a lesser extent in the tunica media, within smooth muscle. Medium (external diameter 200-100 microm) and small-sized (external diameter smaller than 100 microm) pial arteries displayed a significantly higher immune staining than large-sized pial arteries or circle of Willis arteries. The above data that are consistent with recent functional studies reporting cholinergic dilation of cerebral blood vessels mediated via a m5 receptor, have shown that both endothelial and muscular components of cerebral arteries synthesize and express a muscarinic m5 receptor. In view of the peculiar localization in cerebral vessels, handling of the muscarinic m5 receptor may be considered as an approach in the treatment of cerebrovascular disease.
