The effect of the angiotensin converting enzyme (ACE) inhibitor, captopril, on proteosynthesis in the aorta, acetylcholine-stimulated aortic relaxation and endothelaemia (circulating endothelial cells) was investigated in rabbits with aortic insufficiency. The animals were studied 28 days after experimental intervention. Cardiac volume overload stimulated proteosynthesis in the aorta as reflected by increased ribonucleic acid (RNA) concentration and [14C] leucine incorporation into proteins of the aorta. Moreover, the number of endothelial cells in the blood was increased. The administration of captopril starting from the second day of the haemodynamic overload, partially prevented the increase both in aortic proteosynthesis and in endothelaemia. Despite these alterations, the relaxing ability of the aorta to acetylcholine was not changed either by the haemodynamic overload or by captopril. We conclude that the increase of proteosynthesis in the aorta and of endothelaemia in the early period of chronic cardiac volume overload in rabbits were partially prevented by chronic captopril treatment. Neither aortic insufficiency nor captopril changed the acetylcholine-induced relaxation of the aorta.
Heart failure has become the most widely studied syndrome in cardiology over the recent years. Despite the encouraging achievements by angiotensin converting enzyme (ACE) inhibitors, the mortality of patients with chronic heart failure remains high. There are several factors which can potentially be responsible for the fact that about 80% of patients with a failing heart defy protection by ACE inhibitors: different activation of tissue and systemic renin-angiotensin system (RAS) in a particular heart disease and the distinct ability of various ACE inhibitors to block cardiac ACE, alternative pathways for angiotensin II formation (chymase), genetic polymorphism of the RAS system and the complexity of neuroendocrine activation. Moreover, chronic heart failure can provoke disturbances in the reactivity of peripheral vessels and metabolism of striated muscles. These factors may then potentiate the vicious circle of heart failure. New therapeutic approaches, which could further reduce the mortality in patients with heart failure involve angiotensin II type 1 receptor antagonists, beta-blockers, aldosterone antagonists and blockers of the endothelin receptor. A number of questions associated with functions of the RAS still remain open and their solution could be of substantial benefit for patients with a failing heart., F. Šimko, J. Šimko., and Obsahuje bibliografii
Left ventricular hypertrophy (LVH) is the result of interaction between a chronic hemodynamic overload and non-hemodynamic factors. There are several lines of evidence presented in this work suggesting that nitric oxide (NO) may participate in the hypertrophic growth of the myocardium. First, endothelial NO production was shown to be decreased in several types of hemodynamically overloaded circulation both in animals and humans. Second, compounds stimulating NO production were able to diminish the extent or modify the nature of LVH in some models of myocardial hypertrophic growth. Third, arterial hypertension can be induced by inhibition of nitric oxide synthase activity. This NO-deficient hypertension is associated with the development of concentric LVH, myocardial fibrosis and protein remodeling of the left ventricle. The mechanism of LVH development in NO-deficient hypertension is complex and involves decreased NO production and increased activation of the renin-angiotensin-aldosterone system. Cardiovascular protection via ACE inhibition in NO-deficient hypertension may be induced by mechanisms not involving an improvement of NO production. In conclusion, the hypertrophic growth of the LV appears to be the result of interaction of vasoconstrictive and growth stimulating effects of angiotensin II on the one hand and of vasodilating and antiproliferative effects of nitric oxide on the other., F. Šimko, J. Šimko., and Obsahuje bibliografii