Patterns of cardiovascular pathology induced by diverse cardioactive drugs.
In the beagle dog, exaggerated hypotension and tachycardia following administration of high doses of vasodilating antihypertensive drugs are associated with vascular injury and characteristic patterns of myocardial necrosis and haemorrhage. Cardiac and vascular inflammation and necrosis also occur in dogs in association with different functional changes including severe hypertension and the effects that follow treatment with high doses of vasoconstrictor and pressor drugs. More recently, cardioactive drugs of novel classes such as the endothelin antagonists have also been shown to produce vascular damage in the beagle dog but in the absence of ischaemic myocardial damage or significant haemodynamic alterations that typically follow administration of high doses of vasodilating antihypertensive or pressor drugs. This underlines the importance of a careful analysis of the patterns of cardiovascular pathology, their dose, temporal and spatial relationships in the context of functional changes.
Greaves
P
P
Safety of Medicines, AstraZeneca Pharmaceuticals, Mereside, Alderley Park, Cheshire, UK. peter.greaves@alderley.zeneca.com
D000818:Animals; D001167:Arteritis / Q000139:chemically induced* / Q000473:pathology; D002317:Cardiovascular Agents / Q000633:toxicity*; D004285:Dogs; D016232:Endothelins / Q000037:antagonists & inhibitors; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007022:Hypotension / Q000139:chemically induced; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology*
D002317:Cardiovascular Agents; D016232:Endothelins