Decreased Endothelium‐Dependent Hyperpolarization to Acetylcholine in Smooth Muscle of the Mesenteric Artery of Spontaneously Hypertensive Rats
作者:
Koji Fujii,
Mitsuhiro Tominaga,
Susumu Ohmori,
Kazuo Kobayashi,
Tokushi Koga,
Yutaka Takata,
Masatoshi Fujishima,
期刊:
Circulation Research
(OVID Available online 1992)
卷期:
Volume 70,
issue 4
页码: 660-669
ISSN:0009-7330
年代: 1992
出版商: OVID
关键词: membrane potential;endothelium-derived hyperpolarizing factor;acetylcholine;vascular smooth muscle;spontaneously hypertensive rats
数据来源: OVID
摘要:
The endothelium-dependent vascular relaxation to acetylcholine (ACh) in spontaneously hypertensive rats (SHR) may be impaired because of an imbalance of endothelium-derived relaxing factor and contracting factor. However, the role of the endothelium-dependent hyperpolarization remains undetermined. We examined the ACh-induced hyperpolarization and its contribution to relaxation in arteries of SHR. Membrane potentials were recorded from the mesenteric artery trunk of 6–8-month-old male SHR and also Wistar-Kyoto (WKY) rats. Endothelium-dependent hyperpolarization to ACh was unaffected byNG-nitro-l-arginine, indomethacin, or glibenclamide; was reduced by tetraethylammonium or high K+solution; and was enhanced by low K+solution or methylene blue, thereby indicating that hyperpolarization is not mediated by nitric oxide (endothelium-derived relaxing factor) but is presumably mediated by a hyperpolarizing factor and is due to an opening of K+channels that probably differ from the ATP-sensitive ones. Hyperpolarizations to ACh were markedly reduced in SHR compared with findings in WKY rats (maximum, 8±1 versus 17±1 mV). In addition, under conditions of depolarization with norepinephrine (10−5M), the ACh-induced hyperpolarization was even less and transient in SHR, while it was large and sustained in WKY rats (6±1 versus 29±2 mV). Endothelium-dependent relaxations to ACh in arterial rings precontracted with 10−5M norepinephrine were far less in SHR than in WKY rats, even in the presence of indomethacin. Furthermore, high K+solution showed smaller inhibitory effects on the relaxations in SHR than in WKY rats. Endothelium-independent hyperpolarizations and relaxations to cromakalim, a K+channel opener, were similar between SHR and WKY rats. It would thus appear that the endothelium-dependent hyperpolarization to ACh is reduced in SHR and this would, in part, account for the impaired relaxation to ACh in SHR mesenteric arteries.
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