Antihypertensive Mechanism of Orally Administered Acetylcholine in Spontaneously Hypertensive Rats

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 effect...

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Main Authors: Shohei Yamaguchi, Yuzumi Hayasaka, Miho Suzuki, Wenhao Wang, Masahiro Koyama, Yasuko Nagasaka, Kozo Nakamura
Format: Article
Language:English
Published: MDPI AG 2022-02-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/14/4/905
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author Shohei Yamaguchi
Yuzumi Hayasaka
Miho Suzuki
Wenhao Wang
Masahiro Koyama
Yasuko Nagasaka
Kozo Nakamura
author_facet Shohei Yamaguchi
Yuzumi Hayasaka
Miho Suzuki
Wenhao Wang
Masahiro Koyama
Yasuko Nagasaka
Kozo Nakamura
author_sort Shohei Yamaguchi
collection DOAJ
description 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.
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spelling doaj.art-9753979933304952b81a0678703ab7d32023-11-23T21:30:14ZengMDPI AGNutrients2072-66432022-02-0114490510.3390/nu14040905Antihypertensive Mechanism of Orally Administered Acetylcholine in Spontaneously Hypertensive RatsShohei Yamaguchi0Yuzumi Hayasaka1Miho Suzuki2Wenhao Wang3Masahiro Koyama4Yasuko Nagasaka5Kozo Nakamura6Department of Science and Technology, Graduate School of Medicine, Science and Technology, Shinshu University, 8304 Minamiminowa, Nagano 399-4598, JapanDepartment of Agriculture, Graduate School of Science and Technology, Shinshu University, Nagano 399-4598, JapanDepartment of Agriculture, Graduate School of Science and Technology, Shinshu University, Nagano 399-4598, JapanDepartment of Science and Technology, Graduate School of Medicine, Science and Technology, Shinshu University, 8304 Minamiminowa, Nagano 399-4598, JapanWellnas Co., Ltd., Toranomon Masters Building 6F, 1-12-14, Toranomon, Minato-ku, Tokyo 105-0001, JapanDepartment of Anesthesia, Tokyo Women’s Medical University Hospital, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-0054, JapanDepartment of Science and Technology, Graduate School of Medicine, Science and Technology, Shinshu University, 8304 Minamiminowa, Nagano 399-4598, JapanAcetylcholine (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.https://www.mdpi.com/2072-6643/14/4/905acetylcholinehypertensionspontaneously hypertensive ratsympathetic nervous systemtelemetry
spellingShingle Shohei Yamaguchi
Yuzumi Hayasaka
Miho Suzuki
Wenhao Wang
Masahiro Koyama
Yasuko Nagasaka
Kozo Nakamura
Antihypertensive Mechanism of Orally Administered Acetylcholine in Spontaneously Hypertensive Rats
Nutrients
acetylcholine
hypertension
spontaneously hypertensive rat
sympathetic nervous system
telemetry
title Antihypertensive Mechanism of Orally Administered Acetylcholine in Spontaneously Hypertensive Rats
title_full Antihypertensive Mechanism of Orally Administered Acetylcholine in Spontaneously Hypertensive Rats
title_fullStr Antihypertensive Mechanism of Orally Administered Acetylcholine in Spontaneously Hypertensive Rats
title_full_unstemmed Antihypertensive Mechanism of Orally Administered Acetylcholine in Spontaneously Hypertensive Rats
title_short Antihypertensive Mechanism of Orally Administered Acetylcholine in Spontaneously Hypertensive Rats
title_sort antihypertensive mechanism of orally administered acetylcholine in spontaneously hypertensive rats
topic acetylcholine
hypertension
spontaneously hypertensive rat
sympathetic nervous system
telemetry
url https://www.mdpi.com/2072-6643/14/4/905
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