Abstract |
Coronary artery spasm is caused primarily by increased contractility of vascular smooth muscle. Excessive Ca2+ entry into vascular smooth muscle cells (VSMCs) may be one of the key mechanisms for the spasm, but no study has ever directly examined the possible alterations of Ca2+ channels in the spastic coronary artery. Here we show that L-type Ca2+ channels are excessively expressed at the spastic site of the coronary artery. In a porcine model of coronary spasm with balloon injury, both receptor-mediated stimulation of L-type Ca2+ channels by serotonin and direct stimulation of the channels by Bay K 8644 (a dihydropyridine Ca2+ channel agonist) repeatedly induced coronary spasm in vivo, which was abolished by pretreatment with nifedipine, a dihydropyridine Ca2+ channel antagonist. In a single VSMC freshly dispersed from coronary arteries in vitro, patch-clamp experiments showed that current density of L-type Ca2+ channel current was significantly increased in VSMCs from the spastic site compared with that from the control site even when the channels were maximally stimulated by Bay K 8644. There was no difference in the sensitivity of the channels to Bay K 8644. These results indicate that functionally available L-type Ca2+ channels are excessively expressed at the spastic site of the coronary artery in our porcine model, suggesting that increased expression of L-type Ca2+ channels and concomitant increase in Ca2+ entry into VSMCs through the channels may contribute, at least in part, to the pathogenesis of coronary artery spasm.
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Authors | T Kuga, H Shimokawa, Y Hirakawa, Y Kadokami, Y Arai, Y Fukumoto, K Kuwata, T Kozai, K Egashira, A Takeshita |
Journal | Journal of cardiovascular pharmacology
(J Cardiovasc Pharmacol)
Vol. 35
Issue 5
Pg. 822-8
(May 2000)
ISSN: 0160-2446 [Print] United States |
PMID | 10813387
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Calcium Channel Agonists
- Calcium Channels, L-Type
- 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
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Topics |
- 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
(pharmacology)
- Animals
- Calcium Channel Agonists
(pharmacology)
- Calcium Channels, L-Type
(biosynthesis, metabolism)
- Coronary Vasospasm
(chemically induced, metabolism)
- Disease Models, Animal
- Male
- Muscle, Smooth, Vascular
(metabolism)
- Patch-Clamp Techniques
- Swine
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