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Endothelium dependent relaxation in two different models of chronic heart failure and the effect of ibopamine
H Buikema1, W H van Gilst, D J van Veldhuisen
1Department of Pharmacology/Clinical Pharmacology, University of Groningen, The Netherlands.
Objectives:
The purpose was to relate endothelium dependent relaxation to neurohumoral and haemodynamic changes in rats with chronic heart failure.
Methods:
Rats were submitted to either coronary ligation causing myocardial infarction or banding of the abdominal aorta (aortic stenosis), and comparisons were made with normal rats (n = 20 per group). Starting six weeks after surgery, half of the experimental animals received ibopamine and the other half served as controls and were given saline for another three weeks. After this, haemodynamic and neurohumoral variables were determined and the rats were killed. Rings of both the thoracic and abdominal aorta were studied in organ baths to measure their response to vasoactive agents.
Results:
Increased plasma noradrenaline concentrations in rats with myocardial infarction and aortic stenosis 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 maximal relaxation to sodium nitrite was depressed in the thoracic aorta from rats with myocardial infarction. The pIC50 of metacholine induced relaxation was smaller in the thoracic aorta from rats with myocardial infarction and aortic stenosis. By contrast, both pIC50 and the maximal relaxation (Emax) were increased in the abdominal aorta from rats with aortic stenosis, whereas Emax was smaller in rats with myocardial infarction. Ibopamine had no significant effects on these responses.
Conclusions:
Endothelium dependent relaxation to metacholine was selectively altered in rats with chronic heart failure due to aortic stenosis, probably because of differences in regional haemodynamics. In rats with myocardial infarction, however, endothelium dependent relaxation was impaired in both the thoracic and abdominal aorta. Ibopamine acted as a neurohumoral modulator by reducing increased noradrenaline concentrations but had no significant effect on either endothelium dependent or independent relaxation.