Linalyl acetate prevents olmesartan-induced intestinal hypermotility mediated by interference of the sympathetic inhibitory pathway in hypertensive rat

Soonho Kwon, Yu Shan Hsieh, You Kyoung Shin, Purum Kang, Geun Hee Seol

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Olmesartan-associated enteropathy (OAE) is a life-threatening pathological condition, but its underlying mechanisms have not been elucidated. Although intestinal hypermotility is frequently accompanied by chronic diarrhea, there have been no studies of olmesartan-induced hypermotility. Intestinal motility should be well regulated by the enteric nervous system, but degeneration of enteric neurons has been reported in patients with chronic diarrheal diseases, such as irritable bowel syndrome, suggesting a connection between OAE and intestinal hypermotility. In this study, interference with this inhibitory pathway was analyzed in a model of olmesartan-induced intestinal hypermotility (OIH) in rats with nicotine-induced hypertension exposed to chronic immobilizing stress. The effects of the potent inhibitory neurotransmitters norepinephrine (NE) and sodium nitroprusside (SNP), which act via different pathways, were assessed ex vivo, with only NE-modulated frequency and amplitude of spontaneous contractions found to be elevated in OIH rat jejunum. Clinical symptoms frequent in OAE, including atrophy of the intestinal epithelium and weight loss, were observed in these rats. Interestingly, olmesartan significantly elevated heart rate while lowering blood pressure in OIH rats. These abnormal conditions were prevented by adding linalyl acetate (LA), while the blood pressure-lowering effects of olmesartan were maintained. These findings suggest that olmesartan induces intestinal hypermotility by interfering with the sympathetic inhibitory pathway, and reduces epithelial cell size or body weight in hypertensive rats. As LA prevented these effects, combination treatment with olmesartan plus LA may provide better antihypertensive efficacy without inducing OAE.

Original languageEnglish
Pages (from-to)362-368
Number of pages7
JournalBiomedicine and Pharmacotherapy
Volume102
DOIs
Publication statusPublished - 2018 Jun 1

Fingerprint

linalyl acetate
olmesartan
Norepinephrine
Blood Pressure
Enteric Nervous System
Nerve Degeneration
Gastrointestinal Motility
Irritable Bowel Syndrome
Nitroprusside
Jejunum
Intestinal Mucosa
Nicotine
Cell Size
Antihypertensive Agents
Atrophy
Neurotransmitter Agents
Weight Loss
Diarrhea
Chronic Disease
Heart Rate

Keywords

  • Diarrhea
  • Intestinal hypermotility
  • Linalyl acetate
  • Olmesartan
  • Sympathetic inhibitory pathway

ASJC Scopus subject areas

  • Pharmacology

Cite this

Linalyl acetate prevents olmesartan-induced intestinal hypermotility mediated by interference of the sympathetic inhibitory pathway in hypertensive rat. / Kwon, Soonho; Hsieh, Yu Shan; Shin, You Kyoung; Kang, Purum; Seol, Geun Hee.

In: Biomedicine and Pharmacotherapy, Vol. 102, 01.06.2018, p. 362-368.

Research output: Contribution to journalArticle

@article{197e7e2ec1244bdb89ae0513c1c47d40,
title = "Linalyl acetate prevents olmesartan-induced intestinal hypermotility mediated by interference of the sympathetic inhibitory pathway in hypertensive rat",
abstract = "Olmesartan-associated enteropathy (OAE) is a life-threatening pathological condition, but its underlying mechanisms have not been elucidated. Although intestinal hypermotility is frequently accompanied by chronic diarrhea, there have been no studies of olmesartan-induced hypermotility. Intestinal motility should be well regulated by the enteric nervous system, but degeneration of enteric neurons has been reported in patients with chronic diarrheal diseases, such as irritable bowel syndrome, suggesting a connection between OAE and intestinal hypermotility. In this study, interference with this inhibitory pathway was analyzed in a model of olmesartan-induced intestinal hypermotility (OIH) in rats with nicotine-induced hypertension exposed to chronic immobilizing stress. The effects of the potent inhibitory neurotransmitters norepinephrine (NE) and sodium nitroprusside (SNP), which act via different pathways, were assessed ex vivo, with only NE-modulated frequency and amplitude of spontaneous contractions found to be elevated in OIH rat jejunum. Clinical symptoms frequent in OAE, including atrophy of the intestinal epithelium and weight loss, were observed in these rats. Interestingly, olmesartan significantly elevated heart rate while lowering blood pressure in OIH rats. These abnormal conditions were prevented by adding linalyl acetate (LA), while the blood pressure-lowering effects of olmesartan were maintained. These findings suggest that olmesartan induces intestinal hypermotility by interfering with the sympathetic inhibitory pathway, and reduces epithelial cell size or body weight in hypertensive rats. As LA prevented these effects, combination treatment with olmesartan plus LA may provide better antihypertensive efficacy without inducing OAE.",
keywords = "Diarrhea, Intestinal hypermotility, Linalyl acetate, Olmesartan, Sympathetic inhibitory pathway",
author = "Soonho Kwon and Hsieh, {Yu Shan} and Shin, {You Kyoung} and Purum Kang and Seol, {Geun Hee}",
year = "2018",
month = "6",
day = "1",
doi = "10.1016/j.biopha.2018.03.095",
language = "English",
volume = "102",
pages = "362--368",
journal = "Biomedicine and Pharmacotherapy",
issn = "0753-3322",
publisher = "Elsevier Masson",

}

TY - JOUR

T1 - Linalyl acetate prevents olmesartan-induced intestinal hypermotility mediated by interference of the sympathetic inhibitory pathway in hypertensive rat

AU - Kwon, Soonho

AU - Hsieh, Yu Shan

AU - Shin, You Kyoung

AU - Kang, Purum

AU - Seol, Geun Hee

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Olmesartan-associated enteropathy (OAE) is a life-threatening pathological condition, but its underlying mechanisms have not been elucidated. Although intestinal hypermotility is frequently accompanied by chronic diarrhea, there have been no studies of olmesartan-induced hypermotility. Intestinal motility should be well regulated by the enteric nervous system, but degeneration of enteric neurons has been reported in patients with chronic diarrheal diseases, such as irritable bowel syndrome, suggesting a connection between OAE and intestinal hypermotility. In this study, interference with this inhibitory pathway was analyzed in a model of olmesartan-induced intestinal hypermotility (OIH) in rats with nicotine-induced hypertension exposed to chronic immobilizing stress. The effects of the potent inhibitory neurotransmitters norepinephrine (NE) and sodium nitroprusside (SNP), which act via different pathways, were assessed ex vivo, with only NE-modulated frequency and amplitude of spontaneous contractions found to be elevated in OIH rat jejunum. Clinical symptoms frequent in OAE, including atrophy of the intestinal epithelium and weight loss, were observed in these rats. Interestingly, olmesartan significantly elevated heart rate while lowering blood pressure in OIH rats. These abnormal conditions were prevented by adding linalyl acetate (LA), while the blood pressure-lowering effects of olmesartan were maintained. These findings suggest that olmesartan induces intestinal hypermotility by interfering with the sympathetic inhibitory pathway, and reduces epithelial cell size or body weight in hypertensive rats. As LA prevented these effects, combination treatment with olmesartan plus LA may provide better antihypertensive efficacy without inducing OAE.

AB - Olmesartan-associated enteropathy (OAE) is a life-threatening pathological condition, but its underlying mechanisms have not been elucidated. Although intestinal hypermotility is frequently accompanied by chronic diarrhea, there have been no studies of olmesartan-induced hypermotility. Intestinal motility should be well regulated by the enteric nervous system, but degeneration of enteric neurons has been reported in patients with chronic diarrheal diseases, such as irritable bowel syndrome, suggesting a connection between OAE and intestinal hypermotility. In this study, interference with this inhibitory pathway was analyzed in a model of olmesartan-induced intestinal hypermotility (OIH) in rats with nicotine-induced hypertension exposed to chronic immobilizing stress. The effects of the potent inhibitory neurotransmitters norepinephrine (NE) and sodium nitroprusside (SNP), which act via different pathways, were assessed ex vivo, with only NE-modulated frequency and amplitude of spontaneous contractions found to be elevated in OIH rat jejunum. Clinical symptoms frequent in OAE, including atrophy of the intestinal epithelium and weight loss, were observed in these rats. Interestingly, olmesartan significantly elevated heart rate while lowering blood pressure in OIH rats. These abnormal conditions were prevented by adding linalyl acetate (LA), while the blood pressure-lowering effects of olmesartan were maintained. These findings suggest that olmesartan induces intestinal hypermotility by interfering with the sympathetic inhibitory pathway, and reduces epithelial cell size or body weight in hypertensive rats. As LA prevented these effects, combination treatment with olmesartan plus LA may provide better antihypertensive efficacy without inducing OAE.

KW - Diarrhea

KW - Intestinal hypermotility

KW - Linalyl acetate

KW - Olmesartan

KW - Sympathetic inhibitory pathway

UR - http://www.scopus.com/inward/record.url?scp=85044133346&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044133346&partnerID=8YFLogxK

U2 - 10.1016/j.biopha.2018.03.095

DO - 10.1016/j.biopha.2018.03.095

M3 - Article

C2 - 29571021

AN - SCOPUS:85044133346

VL - 102

SP - 362

EP - 368

JO - Biomedicine and Pharmacotherapy

JF - Biomedicine and Pharmacotherapy

SN - 0753-3322

ER -