Attenuation of L-type Ca2+ channel expression and vasomotor response in the aorta with age in both Wistar-Kyoto and spontaneously hypertensive rats

Toshihiko Fukuda, Takahiro Kuroda, Miki Kono, Takahisa Miyamoto, Mitsuru Tanaka, Toshiro Matsui

研究成果: ジャーナルへの寄稿記事

12 引用 (Scopus)

抄録

Age-related vascular diseases are induced by vascular dysfunction, which involves changes in the vasomotor response. The voltage-dependent L-type calcium channel (VDCC) protein is involved in the regulation of vessel function (contraction/ relaxation action). In the present study, we evaluated age-related vasomotor function and expression of the signal-related target proteins, including VDCC, using thoracic aorta from both 8- and 40-week old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). In contraction experiments using aortic rings, vasomotor responses of both phenylephrine-induced contraction and acetylcholine-induced relaxation were significantly attenuated with age in SHR, whereas WKY did not lose activity with age. Contraction induced by angiotensin II was impaired only for the 40-week old SHR among all the rat groups tested, although enhanced AT1R/reduced AT2R expression with age was observed for both WKY and SHR. In contrast, a vasomotor responsiveness to Bay K 8644 (a VDCC agonist) at the initial contraction phase was significantly attenuated in both 40-week WKY and SHR with significant reduction of VDCC protein expression. The reduced VDCC expression in 40-week old rats significantly lowered the relaxation activity of VDCC blockers, such as verapamil and Trp-His, but did not affect that of nifedipine. Taken together, we provided the first evidence that aging caused a reduction of VDCC expression in rat aorta, irrespective of the rat strain, along with diminishment of the therapeutic potential of VDCC blockers.

元の言語英語
記事番号e88975
ジャーナルPloS one
9
発行部数2
DOI
出版物ステータス出版済み - 2 12 2014

Fingerprint

L-Type Calcium Channels
Inbred SHR Rats
aorta
Aorta
Rats
calcium channels
calcium
rats
Calcium Channel Blockers
tryptophyl-histidine
Calcium Channel Agonists
calcium channel blockers
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
Proteins
Phenylephrine
Nifedipine
Verapamil
Thoracic Aorta
Vascular Diseases
Angiotensin II

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

これを引用

Attenuation of L-type Ca2+ channel expression and vasomotor response in the aorta with age in both Wistar-Kyoto and spontaneously hypertensive rats. / Fukuda, Toshihiko; Kuroda, Takahiro; Kono, Miki; Miyamoto, Takahisa; Tanaka, Mitsuru; Matsui, Toshiro.

:: PloS one, 巻 9, 番号 2, e88975, 12.02.2014.

研究成果: ジャーナルへの寄稿記事

@article{b247761e292640b1b3d5ada113babdd0,
title = "Attenuation of L-type Ca2+ channel expression and vasomotor response in the aorta with age in both Wistar-Kyoto and spontaneously hypertensive rats",
abstract = "Age-related vascular diseases are induced by vascular dysfunction, which involves changes in the vasomotor response. The voltage-dependent L-type calcium channel (VDCC) protein is involved in the regulation of vessel function (contraction/ relaxation action). In the present study, we evaluated age-related vasomotor function and expression of the signal-related target proteins, including VDCC, using thoracic aorta from both 8- and 40-week old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). In contraction experiments using aortic rings, vasomotor responses of both phenylephrine-induced contraction and acetylcholine-induced relaxation were significantly attenuated with age in SHR, whereas WKY did not lose activity with age. Contraction induced by angiotensin II was impaired only for the 40-week old SHR among all the rat groups tested, although enhanced AT1R/reduced AT2R expression with age was observed for both WKY and SHR. In contrast, a vasomotor responsiveness to Bay K 8644 (a VDCC agonist) at the initial contraction phase was significantly attenuated in both 40-week WKY and SHR with significant reduction of VDCC protein expression. The reduced VDCC expression in 40-week old rats significantly lowered the relaxation activity of VDCC blockers, such as verapamil and Trp-His, but did not affect that of nifedipine. Taken together, we provided the first evidence that aging caused a reduction of VDCC expression in rat aorta, irrespective of the rat strain, along with diminishment of the therapeutic potential of VDCC blockers.",
author = "Toshihiko Fukuda and Takahiro Kuroda and Miki Kono and Takahisa Miyamoto and Mitsuru Tanaka and Toshiro Matsui",
year = "2014",
month = "2",
day = "12",
doi = "10.1371/journal.pone.0088975",
language = "English",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "2",

}

TY - JOUR

T1 - Attenuation of L-type Ca2+ channel expression and vasomotor response in the aorta with age in both Wistar-Kyoto and spontaneously hypertensive rats

AU - Fukuda, Toshihiko

AU - Kuroda, Takahiro

AU - Kono, Miki

AU - Miyamoto, Takahisa

AU - Tanaka, Mitsuru

AU - Matsui, Toshiro

PY - 2014/2/12

Y1 - 2014/2/12

N2 - Age-related vascular diseases are induced by vascular dysfunction, which involves changes in the vasomotor response. The voltage-dependent L-type calcium channel (VDCC) protein is involved in the regulation of vessel function (contraction/ relaxation action). In the present study, we evaluated age-related vasomotor function and expression of the signal-related target proteins, including VDCC, using thoracic aorta from both 8- and 40-week old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). In contraction experiments using aortic rings, vasomotor responses of both phenylephrine-induced contraction and acetylcholine-induced relaxation were significantly attenuated with age in SHR, whereas WKY did not lose activity with age. Contraction induced by angiotensin II was impaired only for the 40-week old SHR among all the rat groups tested, although enhanced AT1R/reduced AT2R expression with age was observed for both WKY and SHR. In contrast, a vasomotor responsiveness to Bay K 8644 (a VDCC agonist) at the initial contraction phase was significantly attenuated in both 40-week WKY and SHR with significant reduction of VDCC protein expression. The reduced VDCC expression in 40-week old rats significantly lowered the relaxation activity of VDCC blockers, such as verapamil and Trp-His, but did not affect that of nifedipine. Taken together, we provided the first evidence that aging caused a reduction of VDCC expression in rat aorta, irrespective of the rat strain, along with diminishment of the therapeutic potential of VDCC blockers.

AB - Age-related vascular diseases are induced by vascular dysfunction, which involves changes in the vasomotor response. The voltage-dependent L-type calcium channel (VDCC) protein is involved in the regulation of vessel function (contraction/ relaxation action). In the present study, we evaluated age-related vasomotor function and expression of the signal-related target proteins, including VDCC, using thoracic aorta from both 8- and 40-week old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). In contraction experiments using aortic rings, vasomotor responses of both phenylephrine-induced contraction and acetylcholine-induced relaxation were significantly attenuated with age in SHR, whereas WKY did not lose activity with age. Contraction induced by angiotensin II was impaired only for the 40-week old SHR among all the rat groups tested, although enhanced AT1R/reduced AT2R expression with age was observed for both WKY and SHR. In contrast, a vasomotor responsiveness to Bay K 8644 (a VDCC agonist) at the initial contraction phase was significantly attenuated in both 40-week WKY and SHR with significant reduction of VDCC protein expression. The reduced VDCC expression in 40-week old rats significantly lowered the relaxation activity of VDCC blockers, such as verapamil and Trp-His, but did not affect that of nifedipine. Taken together, we provided the first evidence that aging caused a reduction of VDCC expression in rat aorta, irrespective of the rat strain, along with diminishment of the therapeutic potential of VDCC blockers.

UR - http://www.scopus.com/inward/record.url?scp=84895736251&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84895736251&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0088975

DO - 10.1371/journal.pone.0088975

M3 - Article

C2 - 24533163

AN - SCOPUS:84895736251

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 2

M1 - e88975

ER -