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Figure 3 illustrates vasoactive responses to ACh and nitroglycerin (NTG) in isolated rat hearts perfused for 50 min at control flows (15 ml/min) or subjected to ischemia at 2.2 ml/min (to produce an 85% reduction in global coronary flow) for 30 min, followed by 20 min of reperfusion at 15 ml/ min. All hearts were then tested for their dilator capacity to ACh and NTG. In control hearts isolated from rats given 0.9% NaCl (ie, control-I-vehicle), both ACh and NTG produced a full vasorelaxation after addition of U-46619, a TXA* mimetic, at the arrows. However, in hearts subjected to ischemia-reperfusion but given 0.9% NaCl (ie, ischemia + vehicle), ACh produced only a partial vasorelaxation (35%) whereas NTG fully relaxed the coronary vasculature. Not shown are responses to A23187, which also showed a partial vasorelaxation, comparable to that of ACh. These findings indicate an endothelial dysfunction in the rat coronary vasculature following ischemia and reperfusion. Intravenous injection of 10 jig of transforming growth factor-0 (TGF-p) to rats 2 h prior to isolation of the heart protected against ischemia-induced endothelial dysfunction in response to ACh without altering the NTG response. These and other data indicate that TGF-p protects the vasculature by antagonizing the deleterious effects of TNF by a mechanism that may also involve prevention of the formation or action of superoxide radicals. Not only does endothelial dysfunction occur in the coronary circulation upon ischemia-reperfusion, but a very similar situation occurs with hypoxia-reoxygenation. Figure 3. Typical responses to acetylcholine (ACh) and nitroglycerin (NTG) in isolated perfused rat hearts to control perfusion, ischemia + reperfusion, and ischemia+reperfusion in rats given transforming growth factor»0 (TGF-0), 10|ig, 2 h prior to ischemia.