Premium
Impaired endothelium‐dependent relaxation of dog coronary arteries after myocardial ischaemia and reperfusion: prevention by amlodipine, propranolol and allopurinol
Author(s) -
Sobey Christopher G.,
Dalipram Romina A.,
Dusting Gregory J.,
Woodman Owen L.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb09018.x
Subject(s) - medicine , amlodipine , allopurinol , propranolol , ischemia , cardiology , coronary occlusion , endothelium , anesthesia , endothelial dysfunction , acetylcholine , coronary arteries , artery , blood pressure
1 Anaesthetized, open‐chest dogs were subjected to 60 min of left circumflex coronary artery occlusion followed by 90 min of reperfusion. Endothelium‐dependent and ‐independent relaxant responses of the isolated coronary arterial rings were then investigated. 2 The endothelium‐dependent, acetylcholine‐induced relaxation of ischaemic/reperfused arterial rings was significantly attenuated in comparison to control rings (1.9 fold rightward shift, ischaemic/reperfused maximum relaxation = 57 ± 13% of control maximum relaxation; P < 0.05). In contrast, glyceryl trinitrate produced similar relaxant responses in control and ischaemic rings. 3 Pretreatment of dogs with either amlodipine (3 μg kg −1 min −1 , i.v.) or propranolol (1 mg kg −1 , i.v.) completely prevented the postischaemic impairment of endothelium‐dependent relaxant responses (100 ± 3% and 90 ± 5% of control maximum relaxation, respectively). 4 Allopurinol pretreatment (25 mg kg −1 , p.o. 24 h previously, plus 50 mg kg −1 i.v. 5 min before arterial occlusion) partially protected against endothelial dysfunction by preventing the ischaemia‐induced rightward shift of the acetylcholine relaxation curve and increasing the maximum relaxation response (83 ± 7% of control rings). 5 These results confirm that endothelium‐dependent coronary vascular relaxation is impaired by ischaemia and reperfusion, and that the ischaemia‐induced impairment is reduced by pretreatment with amlodipine, propranolol or allopurinol.