The role of voltage-operated and non-voltage-operated calcium channels in endothelin-induced vasoconstriction of rat cerebral arteries
| Autor: | Paul F. Soeding, James Ziogas, Yohannes A. Mamo, Christine E. Wright, James A. Angus |
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| Rok vydání: | 2014 |
| Předmět: |
Cyclopropanes
Male Contraction (grammar) Nifedipine Cerebral arteries chemistry.chemical_element In Vitro Techniques Naphthalenes Calcium Pharmacology Rats Sprague-Dawley Cerebral circulation medicine Animals Drug Interactions Endothelin-1 Voltage-dependent calcium channel Electrical impedance myography Chemistry Imidazoles Cerebral Arteries Calcium Channel Blockers Rats Vasoconstriction Benzimidazoles Calcium Channels medicine.symptom Endothelin receptor |
| Zdroj: | European Journal of Pharmacology. 742:65-73 |
| ISSN: | 0014-2999 |
| Popis: | Endothelin-1 has been identified as a potential mediator in the pathogenesis of ischaemic stroke and cerebral vasospasm. The aim of this study was to analyse the role of voltage-operated calcium channels (VOCC) and non-VOCC in endothelin-1 induced vasoconstriction of rat cerebral arteries. Arterial segments were dissected from different regions of the cerebral circulation and responses assessed using wire myography. Endothelin-1 concentration-contraction curves were constructed in calcium-free medium or in the presence of nifedipine, NNC 55-0396 ((1S,2S)-2-(2-(N-[(3-benzimidazol-2-yl)propyl]-N-methylamino)ethyl)-6-fluoro-1,2,3,4-tetrahydro-1-isopropyl-2-naphtyl cyclopropanecarboxylate dihydrochloride) or SKF 96365 (1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole) to inhibit the l-type VOCC, T-type VOCC and non-VOCC, respectively. Inhibition of the calcium channels or removal of calcium from the medium variably decreased the maximum effects (Emax) of endothelin-1, however its potency (pEC50) was unaltered. Endothelin-1 caused a small contraction (22%) in calcium-free solution. Pre-treatment with nifedipine (1µM) did not affect responses to low concentrations of endothelin-1 but decreased Emax, while NNC 55-0396 (1µM) and SKF 96365 (30-100µM) generally attenuated the endothelin-1-induced contraction. Combination of nifedipine with SKF 96365 further decreased the Emax. The relaxant effect of the calcium channel antagonists was also assessed in pre-contracted arteries. Only nifedipine and SKF 96365 relaxed the arteries pre-contracted with endothelin-1. In conclusion, VOCC and non-VOCC calcium channels are involved in different phases of the endothelin-1 contraction in rat cerebral vessels. T-type VOCC may be involved in contraction induced by low concentrations of endothelin-1, while l-type VOCC mediate the maintenance phase of contraction. VOCC and non-VOCC may work in concert in mediating contraction induced by endothelin-1. |
| Databáze: | OpenAIRE |
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