Onset of a hypotensive effect following ingestion of flavan 3-ols involved in the activation of adrenergic receptors

Akiko Saito, Kodai Inagawa, Rikihiko Ebe, Shinobu Fukase, Yukari Horikoshi, Masahiro Shibata, Naomi Osakabe

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

A lot of epidemiological and intervention studies support the hypotensive action resulting from ingestion of foods rich in flavan 3-ols. However, the mechanisms of this action remain unclear. We have reported previously on the alteration of the micro- and systemic circulations after administration of a flavan 3-ol fraction (FL) derived from cocoa in mammals. We also confirmed that blood catecholamine levels increase significantly after administration of FL. In the present study, we examined whether adrenaline receptors are involved in the hemodynamic changes using several adrenaline receptor (AR) blockers. First, we confirmed that mean blood pressure (MBP) decreased significantly and aortic endothelial nitric oxide synthase (eNOS) levels increased significantly following oral treatment of 10 mg/kg FL for 2 weeks in normal rats compared with vehicle administration. However, these changes were not observed with treatment of 1 mg/kg (-)-epicatechin (EC), which contains nearly equivalent amount of 10 mg/kg FL. Secondly, we observed that a single dose of FL produced different hemodynamic changes, such as a transient elevation in heart rate (HR) after ingestion of 1–100 mg/kg FL, but not with 1 mg/kg EC. Furthermore, although MBP rose transiently after 1 and 10 mg/kg FL, this effect was not observed with 100 mg/kg or 1 mg/kg EC. The increases in HR, MBP, and aortic phosphorylated eNOS (p-eNOS) induced by 10 mg/kg FL were prevented completely by pretreatment with the AR blocker, carvedilol. Combination treatment with 100 mg/kg FL and an α1AR blocker, prazosin, significantly reduced MBP, whereas the elevation in HR was enhanced. In addition, after pretreatment with the β2AR blocker, butoxamine, we observed no significant hemodynamic changes with or without 100 mg/kg FL. Moreover, the combination of 100 mg/kg FL and the α2AR blocker, yohimbine, markedly increased MBP, HR and aortic p-eNOS level. These results suggested that the postprandial hemodynamic changes after a single oral dose of FL were induced by an adrenergic effect. This adrenomimetic activity suggested the involvement of a hypotensive effect of FL.

Original languageEnglish
Pages (from-to)584-592
Number of pages9
JournalFree Radical Biology and Medicine
Volume99
DOIs
Publication statusPublished - 2016 Oct 1

Fingerprint

Blood pressure
Adrenergic Receptors
Hemodynamics
Chemical activation
Catechin
Epinephrine
Nitric Oxide Synthase Type III
Butoxamine
Cocoa
Adrenergic Agonists
Mammals
Yohimbine
Prazosin
Adrenergic Agents
Catecholamines
Rats
Blood

Keywords

  • Adrenergic receptor
  • eNOS
  • Flavan 3-ols
  • Hemodynamics
  • Hypotension

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Onset of a hypotensive effect following ingestion of flavan 3-ols involved in the activation of adrenergic receptors. / Saito, Akiko; Inagawa, Kodai; Ebe, Rikihiko; Fukase, Shinobu; Horikoshi, Yukari; Shibata, Masahiro; Osakabe, Naomi.

In: Free Radical Biology and Medicine, Vol. 99, 01.10.2016, p. 584-592.

Research output: Contribution to journalArticle

@article{ed04e7a632f64df388425b0c908cc873,
title = "Onset of a hypotensive effect following ingestion of flavan 3-ols involved in the activation of adrenergic receptors",
abstract = "A lot of epidemiological and intervention studies support the hypotensive action resulting from ingestion of foods rich in flavan 3-ols. However, the mechanisms of this action remain unclear. We have reported previously on the alteration of the micro- and systemic circulations after administration of a flavan 3-ol fraction (FL) derived from cocoa in mammals. We also confirmed that blood catecholamine levels increase significantly after administration of FL. In the present study, we examined whether adrenaline receptors are involved in the hemodynamic changes using several adrenaline receptor (AR) blockers. First, we confirmed that mean blood pressure (MBP) decreased significantly and aortic endothelial nitric oxide synthase (eNOS) levels increased significantly following oral treatment of 10 mg/kg FL for 2 weeks in normal rats compared with vehicle administration. However, these changes were not observed with treatment of 1 mg/kg (-)-epicatechin (EC), which contains nearly equivalent amount of 10 mg/kg FL. Secondly, we observed that a single dose of FL produced different hemodynamic changes, such as a transient elevation in heart rate (HR) after ingestion of 1–100 mg/kg FL, but not with 1 mg/kg EC. Furthermore, although MBP rose transiently after 1 and 10 mg/kg FL, this effect was not observed with 100 mg/kg or 1 mg/kg EC. The increases in HR, MBP, and aortic phosphorylated eNOS (p-eNOS) induced by 10 mg/kg FL were prevented completely by pretreatment with the AR blocker, carvedilol. Combination treatment with 100 mg/kg FL and an α1AR blocker, prazosin, significantly reduced MBP, whereas the elevation in HR was enhanced. In addition, after pretreatment with the β2AR blocker, butoxamine, we observed no significant hemodynamic changes with or without 100 mg/kg FL. Moreover, the combination of 100 mg/kg FL and the α2AR blocker, yohimbine, markedly increased MBP, HR and aortic p-eNOS level. These results suggested that the postprandial hemodynamic changes after a single oral dose of FL were induced by an adrenergic effect. This adrenomimetic activity suggested the involvement of a hypotensive effect of FL.",
keywords = "Adrenergic receptor, eNOS, Flavan 3-ols, Hemodynamics, Hypotension",
author = "Akiko Saito and Kodai Inagawa and Rikihiko Ebe and Shinobu Fukase and Yukari Horikoshi and Masahiro Shibata and Naomi Osakabe",
year = "2016",
month = "10",
day = "1",
doi = "10.1016/j.freeradbiomed.2016.09.008",
language = "English",
volume = "99",
pages = "584--592",
journal = "Free Radical Biology and Medicine",
issn = "0891-5849",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Onset of a hypotensive effect following ingestion of flavan 3-ols involved in the activation of adrenergic receptors

AU - Saito, Akiko

AU - Inagawa, Kodai

AU - Ebe, Rikihiko

AU - Fukase, Shinobu

AU - Horikoshi, Yukari

AU - Shibata, Masahiro

AU - Osakabe, Naomi

PY - 2016/10/1

Y1 - 2016/10/1

N2 - A lot of epidemiological and intervention studies support the hypotensive action resulting from ingestion of foods rich in flavan 3-ols. However, the mechanisms of this action remain unclear. We have reported previously on the alteration of the micro- and systemic circulations after administration of a flavan 3-ol fraction (FL) derived from cocoa in mammals. We also confirmed that blood catecholamine levels increase significantly after administration of FL. In the present study, we examined whether adrenaline receptors are involved in the hemodynamic changes using several adrenaline receptor (AR) blockers. First, we confirmed that mean blood pressure (MBP) decreased significantly and aortic endothelial nitric oxide synthase (eNOS) levels increased significantly following oral treatment of 10 mg/kg FL for 2 weeks in normal rats compared with vehicle administration. However, these changes were not observed with treatment of 1 mg/kg (-)-epicatechin (EC), which contains nearly equivalent amount of 10 mg/kg FL. Secondly, we observed that a single dose of FL produced different hemodynamic changes, such as a transient elevation in heart rate (HR) after ingestion of 1–100 mg/kg FL, but not with 1 mg/kg EC. Furthermore, although MBP rose transiently after 1 and 10 mg/kg FL, this effect was not observed with 100 mg/kg or 1 mg/kg EC. The increases in HR, MBP, and aortic phosphorylated eNOS (p-eNOS) induced by 10 mg/kg FL were prevented completely by pretreatment with the AR blocker, carvedilol. Combination treatment with 100 mg/kg FL and an α1AR blocker, prazosin, significantly reduced MBP, whereas the elevation in HR was enhanced. In addition, after pretreatment with the β2AR blocker, butoxamine, we observed no significant hemodynamic changes with or without 100 mg/kg FL. Moreover, the combination of 100 mg/kg FL and the α2AR blocker, yohimbine, markedly increased MBP, HR and aortic p-eNOS level. These results suggested that the postprandial hemodynamic changes after a single oral dose of FL were induced by an adrenergic effect. This adrenomimetic activity suggested the involvement of a hypotensive effect of FL.

AB - A lot of epidemiological and intervention studies support the hypotensive action resulting from ingestion of foods rich in flavan 3-ols. However, the mechanisms of this action remain unclear. We have reported previously on the alteration of the micro- and systemic circulations after administration of a flavan 3-ol fraction (FL) derived from cocoa in mammals. We also confirmed that blood catecholamine levels increase significantly after administration of FL. In the present study, we examined whether adrenaline receptors are involved in the hemodynamic changes using several adrenaline receptor (AR) blockers. First, we confirmed that mean blood pressure (MBP) decreased significantly and aortic endothelial nitric oxide synthase (eNOS) levels increased significantly following oral treatment of 10 mg/kg FL for 2 weeks in normal rats compared with vehicle administration. However, these changes were not observed with treatment of 1 mg/kg (-)-epicatechin (EC), which contains nearly equivalent amount of 10 mg/kg FL. Secondly, we observed that a single dose of FL produced different hemodynamic changes, such as a transient elevation in heart rate (HR) after ingestion of 1–100 mg/kg FL, but not with 1 mg/kg EC. Furthermore, although MBP rose transiently after 1 and 10 mg/kg FL, this effect was not observed with 100 mg/kg or 1 mg/kg EC. The increases in HR, MBP, and aortic phosphorylated eNOS (p-eNOS) induced by 10 mg/kg FL were prevented completely by pretreatment with the AR blocker, carvedilol. Combination treatment with 100 mg/kg FL and an α1AR blocker, prazosin, significantly reduced MBP, whereas the elevation in HR was enhanced. In addition, after pretreatment with the β2AR blocker, butoxamine, we observed no significant hemodynamic changes with or without 100 mg/kg FL. Moreover, the combination of 100 mg/kg FL and the α2AR blocker, yohimbine, markedly increased MBP, HR and aortic p-eNOS level. These results suggested that the postprandial hemodynamic changes after a single oral dose of FL were induced by an adrenergic effect. This adrenomimetic activity suggested the involvement of a hypotensive effect of FL.

KW - Adrenergic receptor

KW - eNOS

KW - Flavan 3-ols

KW - Hemodynamics

KW - Hypotension

UR - http://www.scopus.com/inward/record.url?scp=84988600829&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84988600829&partnerID=8YFLogxK

U2 - 10.1016/j.freeradbiomed.2016.09.008

DO - 10.1016/j.freeradbiomed.2016.09.008

M3 - Article

C2 - 27616615

AN - SCOPUS:84988600829

VL - 99

SP - 584

EP - 592

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

ER -