Prevention of ischaemia-induced coronary vascular dysfunction.
Myocardial ischaemia and reperfusion cause dysfunction of the coronary vasculature leading to a sustained reduction in coronary blood flow and an impairment of responses to both endothelium-dependent and endothelium-independent vasodilators. In contrast, when previously ischaemic arteries are removed from the myocardium and vascular function is examined in vitro, it is evident that while endothelial function is impaired, smooth muscle reactivity remains intact. Therefore, other changes must be responsible for the general reduction in vasodilator reserve. Examination of the vasculature in the ischaemic myocardium by electron microscopy reveals adhesion of leukocytes and plugging of capillaries. There also is evidence that polymorphonuclear leukocytes (PMNs) release a factor that constricts coronary arterioles, and that release of this factor is increased by atherosclerosis. The identity of this factor remains uncertain, but the calcium antagonist amlodipine prevents the coronary vasoconstriction. Amlodipine is also able to prevent the impaired perfusion and the reduction in vasodilator reserve that occurs after myocardial ischaemia and reperfusion in the dog. In addition, amlodipine prevents the endothelial dysfunction observed in isolated arteries after ischaemia and reperfusion. The interaction between the endothelium and activated PMNs may be a suitable target for pharmacological intervention to improve postischaemic vascular function.
Woodman
O L
OL
Department of Pharmacology, University of Melbourne, Parkville Victoria, Australia. o.woodman@pharmacology.unimelb.edu.au
Hart
J L
JL
Sobey
C G
CG
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001783:Blood Flow Velocity; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D005260:Female; D008297:Male; D008854:Microscopy, Electron; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D017202:Myocardial Ischemia / Q000150:complications*; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers