IMPAIRMENT OF ENDOTHELIUM DEPENDENT RESPONSES IN A RAT MODEL OF CHRONIC HEART-FAILURE - EFFECTS OF AN EXERCISE TRAINING PROTOCOL

Objective: The aim was to document the response of aortic rings from a rat model of heart failure to endothelium dependent and endothelium independent vasodilating agents. The effects of an exercise training schedule upon these responses was studied. Methods: Heart failure was produced in one group of female Wistar rats by coronary artery occlusion, and sham operations were performed in a matched group. The rats were allowed to recover for six weeks, following which half the rats with heart failure were started on a treadmill exercise schedule for a further six weeks. After this time the rats were killed, and rings of aorta were studied in an organ bath to measure the response to both endothelium dependent and endothelium independent vasoactive agents. Results: The presence of heart failure was confirmed in both the non-trained (NT, n=5) and trained rats (TR, n=5), but not in the sham operated animals (SH, n=6). The constrictor response to prostaglandin F2-alpha was similar in aortic rings from all the animals. The relaxation response to the endothelium dependent vasodilator acetylcholine (10(-7) and 10(-6)M was impaired in the rats with heart failure compared to the sham operated animals (10% v 33% with 10(-7)M acetylcholine, p<0.005). The dilator response in the trained rats was not significantly greater than in the non-trained rats (TR 35% v NT 24% with 10(-6) acetylcholine). There was no difference in the response to sodium nitroprusside (10(-7) and 10(-6)M) between the three groups. Conclusions: Chronic heart failure impairs the response of aortic rings to the endothelium dependent vasodilator acetylcholine in a rat model of heart failure. The response to sodium nitroprusside, an endothelium independent relaxing agent, is not impaired by heart failure. These findings may help to explain the raised systemic vascular resistance and the failure of vasodilatation in skeletal muscle vasculature which limits exercise capacity in subjects with heart failure.