Abstract
Language | English |
---|---|
Pages | 716-723 |
Number of pages | 7 |
Journal | British Journal of Pharmacology |
Volume | 157 |
Issue number | 5 |
DOIs | |
Publication status | Published - Jul 2009 |
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Keywords
- mast cell degranulation
- endothelin-1
- myocardial ischaemia
- arrhythmias
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Mast cell degranulation - a mechanism for the anti-arrhythmic effect of endothelin-1? / Walsh, S.K.; Kane, K.A.; Wainwright, C.L.
In: British Journal of Pharmacology, Vol. 157, No. 5, 07.2009, p. 716-723.Research output: Contribution to journal › Article
TY - JOUR
T1 - Mast cell degranulation - a mechanism for the anti-arrhythmic effect of endothelin-1?
AU - Walsh, S.K.
AU - Kane, K.A.
AU - Wainwright, C.L.
PY - 2009/7
Y1 - 2009/7
N2 - The aim of this study was to investigate whether the previously reported anti-arrhythmic effect of endothelin-1 (ET-1) is mediated by degranulation of cardiac mast cells prior to myocardial ischaemia. Male Sprague-Dawley rats received either ET-1 (1.6 nmol·kg−1) in the presence or absence of disodium cromoglycate (DSCG; 20 mg·kg−1·h−1) prior to coronary artery occlusion (CAO). In separate experiments rats were given compound 48/80 (50 µg·kg−1) to compare the effects of ET-1 with those of a known mast cell degranulator. Ischaemia-induced ventricular arrhythmias were detected through continuous monitoring of a lead I electrocardiogram. After 30 min of CAO, the hearts were removed and mast cell degranulation determined by histological analysis. A parallel series of sham groups were performed to determine the direct effects of ET-1 and compound 48/80 on mast cell degranulation in the absence of ischaemia. ET-1 and compound 48/80 both exerted profound anti-arrhythmic effects, significantly reducing the total number of ventricular ectopic beats (P < 0.001) and the incidence of ventricular fibrillation (P < 0.05). These anti-arrhythmic effects were abolished by concomitant DSCG infusion prior to CAO. In sham animals ET-1 and compound 48/80 both induced mast cell degranulation (P < 0.001), an effect which was abolished by DSCG, confirming their ability to induce degranulation of mast cells. These results demonstrate for the first time that when given prior to ischaemia ET-1 mediates its anti-arrhythmic effects, at least in part, via cardiac mast cell degranulation.
AB - The aim of this study was to investigate whether the previously reported anti-arrhythmic effect of endothelin-1 (ET-1) is mediated by degranulation of cardiac mast cells prior to myocardial ischaemia. Male Sprague-Dawley rats received either ET-1 (1.6 nmol·kg−1) in the presence or absence of disodium cromoglycate (DSCG; 20 mg·kg−1·h−1) prior to coronary artery occlusion (CAO). In separate experiments rats were given compound 48/80 (50 µg·kg−1) to compare the effects of ET-1 with those of a known mast cell degranulator. Ischaemia-induced ventricular arrhythmias were detected through continuous monitoring of a lead I electrocardiogram. After 30 min of CAO, the hearts were removed and mast cell degranulation determined by histological analysis. A parallel series of sham groups were performed to determine the direct effects of ET-1 and compound 48/80 on mast cell degranulation in the absence of ischaemia. ET-1 and compound 48/80 both exerted profound anti-arrhythmic effects, significantly reducing the total number of ventricular ectopic beats (P < 0.001) and the incidence of ventricular fibrillation (P < 0.05). These anti-arrhythmic effects were abolished by concomitant DSCG infusion prior to CAO. In sham animals ET-1 and compound 48/80 both induced mast cell degranulation (P < 0.001), an effect which was abolished by DSCG, confirming their ability to induce degranulation of mast cells. These results demonstrate for the first time that when given prior to ischaemia ET-1 mediates its anti-arrhythmic effects, at least in part, via cardiac mast cell degranulation.
KW - mast cell degranulation
KW - endothelin-1
KW - myocardial ischaemia
KW - arrhythmias
UR - http://dx.doi.org/10.1111/j.1476-5381.2009.00222.x
U2 - 10.1111/j.1476-5381.2009.00222.x
DO - 10.1111/j.1476-5381.2009.00222.x
M3 - Article
VL - 157
SP - 716
EP - 723
JO - British Journal of Pharmacology
T2 - British Journal of Pharmacology
JF - British Journal of Pharmacology
SN - 0007-1188
IS - 5
ER -