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 management of heart failure. The benefits include symptomatic relief, improvement in left ventricular function, prevention of progressive ventricular dilation, improved survival and decreased incidence of myocardial infarction and unstable angina.
Ang II antagonists are expected to produce similar beneficial effects to those of ACE inhibitors, through blockade of vascular, adrenal, renal and prejunctional neuronal Ang II type 1 receptors.
Despite similarities between ACE inhibitors and Ang II inhibitors with respect to the 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 angioedema and cough) may be less frequent in patients treated with an Ang II antagonist. ACE inhibitors act within the renin-angiotensin system to prevent the conversion of Ang I to Ang II. Recently, however, enzymes have been described which are capable of producing Ang II via metabolic pathways independent of the classical renin-angiotensin system route.


CONCLUSIONS
At the tissue level, Ang II may still be generated in a patient receiving systemic ACE inhibitor therapy. Ang II blockade at the receptor level may thus be more efficient than ACE inhibition in blocking the undesirable cardiovascular actions of Ang II.
Rush
J E
JE
Merck Research Laboratories, West Point, Pennsylvania.
Rajfer
S I
SI
D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use; D002303:Cardiac Output, Low / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D019808:Losartan; D013777:Tetrazoles / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D019808:Losartan