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Mechanisms of the antispasmodic activity of 3,5-di-t-butyl catechol (DTCAT) on rat vascular smooth muscles.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2007 Apr 30; Vol. 561 (1-3), pp. 112-20. Date of Electronic Publication: 2007 Jan 19. - Publication Year :
- 2007
-
Abstract
- In skeletal muscle sarcoplasmic reticulum vesicles, 3,5-di-t-butyl catechol (DTCAT) promotes the release of Ca(2+) through the activation of ryanodine receptor Ca(2+) channels. DTCAT mechanical and electrophysiological effects have now been investigated in rat aorta rings and single tail artery myocytes. Rat aorta rings incubated with either 30 microM ryanodine or 100 microM DTCAT developed tension, which averaged 36% and 7%, respectively, of that induced by phenylephrine. DTCAT reduced concentration-dependently both aorta ring contractions to high K(+) (IC(50)=13.5 microM) and L-type Ba(2+) current (IC(50)=22.0 microM) in isolated myocytes. Tetraethylammonium did not reverse the antispasmodic effect of DTCAT in rings stimulated with either 25 or 60 mM K(+). DTCAT relaxed concentration-dependently phenylephrine-pre-contracted rings with intact endothelium (IC(50)=10.9 microM). This effect was markedly reduced by pre-incubation of rings with 100 microM Nomega-nitro-l-arginine methyl ester. DTCAT antagonised phenylephrine-induced contractions in endothelium-deprived rings, either in the presence or in the absence of ryanodine (IC(50)=18.7 microM and 39.8 microM, respectively). Furthermore, both DTCAT (IC(50)=53.3 microM) and ryanodine reduced significantly the response to phenylephrine in the absence of extracellular Ca(2+). Phenylephrine-stimulated influx of extracellular Ca(2+) was markedly inhibited when tissues were pre-treated with DTCAT (IC(50)=19.0 microM) as well as nifedipine. DTCAT (>100 microM) was also able to antagonise the contractions induced by phorbol 12-myristate, 13-acetate. In conclusion, this is the first demonstration that DTCAT inhibits vascular smooth muscle voltage-operated Ca(2+) channels and promotes the release of endothelial nitric oxide. Ryanodine receptor Ca(2+) channels activation or the impairment of the contractile apparatus by DTCAT seem to play a secondary role in its vascular activity.
- Subjects :
- Animals
Aorta drug effects
Aorta metabolism
Calcium Channels metabolism
Dose-Response Relationship, Drug
Electrophysiology
Endothelium, Vascular drug effects
Endothelium, Vascular metabolism
Male
Muscle, Smooth, Vascular metabolism
Myocytes, Smooth Muscle drug effects
Myocytes, Smooth Muscle metabolism
Nitric Oxide metabolism
Rats
Rats, Sprague-Dawley
Ryanodine pharmacology
Ryanodine Receptor Calcium Release Channel drug effects
Ryanodine Receptor Calcium Release Channel metabolism
Spasm drug therapy
Calcium metabolism
Calcium Channels drug effects
Catechols pharmacology
Muscle Contraction drug effects
Muscle, Smooth, Vascular drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2999
- Volume :
- 561
- Issue :
- 1-3
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 17292353
- Full Text :
- https://doi.org/10.1016/j.ejphar.2006.12.025