Modulation of coronary circulation and the cardiac matrix by the renin-angiotensin system.

There are short-term and long-term modulations of cardiac function and cardiac composition by the endocrine and paracrine renin-angiotensin system. First, there is an enhancement of coronary vasoconstrictor tone in severe congestive heart failure due to stimulation of this system. Therapeutic interventions that block the RA-system are able to reduce the increased resistance to coronary flow. Second, there is a relationship between the occurrence of arrhythmias and the degree of sympathetic stimulation in congestive heart failure. The renin-angiotensin system may be involved in arrhythmogenesis because of presynaptic modulation of sympathetic neurotransmitter release. However, in the isolated perfused rat heart no class-specific antiarrhythmic properties could be found for ACE inhibitors during progressive myocardial ischaemia. Third, proliferation of the neointima following injury of a coronary artery is at least in part mediated by angiotensin II. Although ACE inhibition was an effective tool in animal experiments to prevent excessive proliferation of the neointima following ballooning, it was less effective in preventing restenosis in man following a repeat coronary angioplasty. Fourth, preferential proliferation of the cardiac interstitium in experimental hypertension has been associated with activation of the renin-angiotensin system. In patients with essential hypertension ACE inhibitors were not only capable of controlling blood pressure but also of normalizing the previously pathological pattern of diastolic left ventricular filling. In summary, by therapeutic intervention that cause a blockade of this system, cardioprotective and cardioreparative processes can be supported.