Increased expression of L-type calcium channels in vascular smooth muscle cells at spastic site in a porcine model of coronary artery spasm
| Autor: | Takeshi Kuga, Kouichi Kuwata, Akira Takeshita, Yoshihiro Fukumoto, Toshiyuki Kozai, Hiroaki Shimokawa, Yoshiaki Kadokami, Yukinori Arai, Kensuke Egashira, Yoji Hirakawa |
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| Rok vydání: | 2000 |
| Předmět: |
Male
medicine.medical_specialty Vascular smooth muscle Patch-Clamp Techniques Calcium Channels L-Type Swine chemistry.chemical_element Coronary Vasospasm Calcium Muscle Smooth Vascular Contractility Internal medicine Medicine Animals L-type calcium channel Pharmacology business.industry Vascular disease Anatomy 3-Pyridinecarboxylic acid 1 4-dihydro-2 6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)- Methyl ester medicine.disease Pathophysiology Electrophysiology Calcium Channel Agonists Disease Models Animal medicine.anatomical_structure chemistry Cardiology Cardiology and Cardiovascular Medicine business Artery |
| Zdroj: | Journal of cardiovascular pharmacology. 35(5) |
| ISSN: | 0160-2446 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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