The effect of sulfinpyrazone on morphological changes in the coronary vasculature induced by prolonged unpredictable stress in the rat.

It was confirmed that prolonged unpredictable stress in the rat induces morphological change in the coronary microcirculation. These changes include dilation in venules, deposits staining positive with PAS in the venules due to platelet aggregation and a breakdown of the endothelial lining in arterioles. Sulfinpyrazone is reported to prevent platelet agglutination, and shows effectiveness in the clinic in preventing re-infarction following infarction. Accordingly rats were exposed to the stress regimen for 50 days, and groups were treated with sulfinpyrazone, either prophylactically (receive drug for 50 days) or therapeutically (receive drug Day 30 to Day 50). The morphology of the hearts of treated animals were compared with those of placebo treated controls. It was demonstrated that therapeutic sulfinpyrazone did not prevent (p less than 0.01), but reduced the incidence of morphological change in the coronary microcirculation. Prophylactic sulfinpyrazone had a distinct protective effect (p less than 0.001). It was demonstrated that the plasma corticosterone levels in both drug groups did not fall to the level found in control groups. The results are discussed in terms of a glucocorticoid-sulfinpyrazone interaction preventing prostaglandin release which will prevent platelet aggregation. It is possible that the interaction relates to maintaining the integrity of the microcirculatory endothelial cells, thus preventing the local release of inflammatory substances.