Volume 1, Number 2, June 2000

Persistent formation of angiotensin II despite treatment with maximally recommended doses of angiotensin converting enzyme inhibitors in patients with chronic heart failure
Sam Hanon, Pugazhendi Vijayaraman, Edmund H Sonnenblick, Thierry H Le Jemtel

Plasma levels of Angiotensin II (Ang II) rise during long-term administration of angiotensin-converting enzyme (ACE) inhibitors in patients with chronic heart failure (CHF). The rise in Ang II plasma levels indicate that, despite ACE inhibition, the renin-angiotensin-aldosterone system (RAAS) remains persistently elevated in these patients. The added benefits of Ang II type I (AT₁)-receptor antagonists in patients with CHF who are already treated with ACE inhibitors (ACE-I) also point to persistent activation of RAAS.
The mechanisms that are responsible for persistent RAAS activation are incomplete inhibition of ACE by current doses of ACE-I and/or continued Ang II formation via pathways other than ACE. Accordingly, the level of ACE inhibition was assessed in 42 patients with CHF treated with maximal doses of ACE-I, by the pressure response to ascending doses of angiotensin I (Ang I). The pressure response to Ang I was measured before and 2 hours after 80 mg of valsartan. In all patients the pressure response to Ang I was lower after administration of valsartan. In 11 patients treated with 80 mg of lisinopril or fosinopril for one week, the pressure response to Ang I was unaltered by valsartan. Thus current doses of ACE-I do not achieve complete inhibition of ACE in patients with CHF.

JRAAS 2000;1:147-150.

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