Abstract
Acetylcholine (ACh) acts as a neurotransmitter and neuromodulator. A small dose of eggplant powder rich in ACh (equivalent to 22 g fresh eggplant/d) has been shown to reduce blood pressure (BP) in individuals with higher BP. Here, we investigated the mechanisms underlying the antihypertensive effects of low-dose orally administered ACh in spontaneously hypertensive rats (SHRs). The effects of ACh on BP and sympathetic nervous activity (SNA), including lumbar SNA (LSNA) and renal SNA (RSNA), were evaluated by subjecting conscious SHRs to a telemetry method. Single oral administration of ACh decreased LSNA and lowered BP. Repeated oral administration of ACh for 30 d decreased RSNA and suppressed the elevated BP. Noradrenaline levels in the urine also decreased. However, vagotomy and co-administration of M3 muscarinic ACh receptor antagonist reversed the BP-lowering effect; the dynamics of non-absorbable orally administered ACh was revealed using stable isotope-labeled ACh. In conclusion, ACh acts on the gastrointestinal M3 muscarinic ACh receptor to increase afferent vagal nerve activity, which decreases SNA by autonomic reflex, suppressing noradrenaline release and lowering BP. This study suggests the use of exogenous ACh as an antihypertensive food supplement for controlling the autonomic nervous system, without absorption into the blood.
Highlights
Acetylcholine (ACh) is an essential endogenous neurotransmitter in several animal taxa [1,2]
blood pressure (BP) elevation was significantly suppressed by orally administered ACh from days 7 to 30 (Figure 1a,b)
renal SNA (RSNA) was significantly suppressed by oral ACh from days 11 to 30, it was almost the same between the two groups for the first 7 d (Figure 1c)
Summary
Acetylcholine (ACh) is an essential endogenous neurotransmitter in several animal taxa [1,2]. Cholinergic nerves develop throughout the body, including the brain, visceral organs, and systemic skeletal muscles. ACh is among the most important endogenous factors that control neural activity in living organisms [3]. The cholinergic system, including ACh receptors and ACh-metabolizing enzymes, is locally expressed in mammalian tissues (except the nervous system) and even on the inner-body surface, i.e., gastrointestinal mucosa, suggesting that ACh has non-neural and exogenous actions [4,5]. Eggplant-derived ACh (dose: 2.3 mg/d) ameliorated higher blood pressure (BP) in a randomized control trial [6], revealing that exogenous ACh is useful as a functional food substance. ACh is typically ingested from foods derived from animals with cholinergic systems, but vegetables and fermented foods can serve as sources of ACh [7]. It was estimated that the ACh present in 61 g of eggplant is equivalent to the effective dose of
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