THEORETICAL BASIS FOR THE USE OF ANGIOTENSIN-II ANTAGONISTS IN THE TREATMENT OF HEART-FAILURE

Therapeutic use of angiotensin converting enzyme (ACE) inhibitors: ACE inhibitors are now accepted as valuable therapeutic agents in the man agement of heart failure. The benefits include symptomatic relief, imp rovement in left ventricular function, prevention of progressive ventr icular dilation, improved survival and decreased incidence of myocardi al infarction and unstable angina. Potential of angiotensin (Ang) II a ntagonists: Ang II antagonists are expected to produce similar benefic ial effects to those of ACE inhibitors, through blockade of vascular, adrenal, renal and prejunctional neuronal Ang II type 1 receptors. Dif ferences between Ang II antagonists and ACE inhibitors: Despite simila rities between ACE inhibitors and Ang II inhibitors with respect to th e mechanism of action, there are theoretical differences which may be of clinical importance. Adverse effects seen with ACE inhibitors that are attributed to non-renin-angiotensin system effects (notably angioe dema and cough) may be less frequent in patients treated with an Ang I I antagonist. ACE inhibitors act within the renin-angiotensin system t o prevent the conversion of Ang I to Ang II. Recently, however, enzyme s have been described which are capable of producing Ang II via metabo lic pathways independent of the classical renin-angiotensin system rou te. Conclusions: At the tissue level, Ang II may still be generated in a patient receiving systemic ACE inhibitor therapy. Ang II blockade a t the receptor level may thus be more efficient than ACE inhibition in blocking the undesirable cardiovascular actions of Ang II.