Impaired endothelium-dependent relaxation of dog coronary arteries after myocardial ischaemia and reperfusion: prevention by amlodipine, propranolol and allopurinol.
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 less than 0.05). In contrast, glyceryl trinitrate produced similar relaxant responses in control and ischaemic rings. 3. Pretreatment of dogs with either amlodipine (3 micrograms 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.
Sobey
C G
CG
Department of Physiology, University of Melbourne, Parkville, Victoria, Australia.
Dalipram
R A
RA
Dusting
G J
GJ
Woodman
O L
OL
D000109:Acetylcholine / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology*; D017311:Amlodipine; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003327:Coronary Disease / Q000503:physiopathology*; D003331:Coronary Vessels / Q000503:physiopathology; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D017311:Amlodipine; D000493:Allopurinol; D011433:Propranolol; D005996:Nitroglycerin; D009543:Nifedipine; D000109:Acetylcholine