Immobilization stress inhibits intimal fibromuscular proliferation in the process of arterial remodeling in rats.
We investigated role of beta-endorphin (END), which is released by immobilization stress, on intimal fibromuscular proliferation in a rat model of arterial remodeling after intimal injury. The endothelium of the abdominal aorta of Wistar-Kyoto rats was denuded, and the rats were subjected to immobilization stress (6 h/d), which raised the serum concentration of END, and intraperitoneal administration of either END (20 ng/kg/d) or naltrexone (NAL: 4 mg/kg/d). The proliferative activity (PA) of medial smooth muscle cells (SMCs) and the intima/media area ratio (R) were determined at 3 and 14 d after denudation, respectively. PA and R were significantly reduced by immobilization (PA: 64.8%, R: 34.6%), and NAL treatment completely reversed the decreases in PA and R. On the other hand, END reduced both PA and R (PA: 21.7% and R: 24.9%), and NAL also reversed the decreases in PA and R. END (20 pg/mL) inhibited both the proliferation (79% at 96 h) and migration (26%) of SMCs cultured with 5% fetal bovine serum in vitro, and NAL (100 microg/mL) reversed the inhibition of both activities. Our results suggest that immobilization stress stimulates the release of endogenous END, which then prevents both proliferation and migration of medial SMCs after intimal injury.
Iwai
Kunimitsu
K
Department of Geriatric Medicine, Kanazawa Medical University, Ishikawa, Japan.
Takahashi
Takashi
T
Nakahashi
Takeshi
T
Nomura
Koji
K
Atsumi
Mikiko
M
Zeng
Li
L
Ishigami
Keiichiro
K
Kanda
Tsugiyasu
T
Yamaguchi
Nobuo
N
Morimoto
Shigeto
S
D000818:Animals; D001012:Aorta, Abdominal / Q000166:cytology* / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D019417:Hindlimb Suspension / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000502:physiology; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D013312:Stress, Physiological / Q000503:physiopathology; D017539:Tunica Intima / Q000166:cytology; D017540:Tunica Media / Q000166:cytology; D001615:beta-Endorphin / Q000097:blood
D009292:Narcotic Antagonists; D018377:Neurotransmitter Agents; D009271:Naltrexone; D001615:beta-Endorphin