ENDOTHELIUM-DEPENDENT RELAXATION IN 2 DIFFERENT MODELS OF CHRONIC HEART-FAILURE AND THE EFFECT OF IBOPAMINE

Objectives: The purpose was to relate endothelium dependent relaxation to neurohumoral and haemodynamic changes in rats with chronic heart f ailure. Methods: Rats were submitted to either coronary ligation causi ng myocardial infarction or banding of the abdominal aorta (aortic ste nosis), and comparisons were made with normal rats (n=20 per group). S tarting six weeks after surgery, half of the experimental animals rece ived ibopamine and the other half served as controls and were given sa line for another three weeks. After this, haemodynamic and neurohumora l variables were determined and the rats were killed. Rings of both th e thoracic and abdominal aorta were studied in organ baths to measure their response to vasoactive agents. Results: Increased plasma noradre naline concentrations in rats with myocardial infarction and aortic st enosis were reduced by ibopamine. Blood pressure and heart rate, which were higher in rats with aortic stenosis than in rats with myocardial infarction and in normal rats, were unaffected by ibopamine. The maxi mal relaxation to sodium nitrite was depressed in the thoracic aorta f rom rats with myocardial infarction. The pIC(50) of metacholine induce d relaxation was smaller in the thoracic aorta from rats with myocardi al infarction and aortic stenosis. By contrast, both pIC(50) and the m aximal relaxation (Emax) were increased in the abdominal aorta from ra ts with aortic stenosis, whereas Emax was smaller in rats with myocard ial infarction. Ibopamine had no significant effects on these response s. Conclusions: Endothelium dependent relaxation to metacholine was se lectively altered in rats with chronic heart failure due to aortic ste nosis, probably because of differences in regional haemodynamics. In r ats with myocardial infarction, however, endothelium dependent relaxat ion was impaired in both the thoracic and abdominal aorta. Ibopamine a cted as a neurohumoral modulator by reducing increased noradrenaline c oncentrations but had no significant effect on either endothelium depe ndent or independent relaxation.