Hemodynamic Effects of Renin Inhibitors

Abstract

Renin inhibitors may offer an exciting new therapeutic means of blocking the actions of the renin-angiotensin-aldosterone system. These compounds interfere with the first, rate-limiting step in the synthesis of angiotensin II by binding directly to the highly specific enzyme, renin. This approach may represent a more focused alternative to angiotensin-converting enzyme inhibitor therapy with an improved side-effect profile. Renin inhibitors given parenterally safely lower blood pressure in patients with essential hypertension and improve the hemodynamic profile of patients with congestive heart failure. Under conditions of salt limitation, normal subjects show increases in renal plasma flow during infusion of renin inhibitors. The systemic and renal hemodynamic responses to renin inhibition are accompanied by suppression of plasma renin activity, plasma angiotensin II and plasma aldosterone levels. Recent scientific advances in discovering how to address the limitations of the low oral bioavailability of peptide-based compounds have made it possible to invent orally active renin inhibitors. Orally active renin inhibitors are presently being evaluated in clinical trials. The availability of intravenous and oral delivery of renin inhibitors broadens the potential of these agents to treat a wide variety of acute and chronic cardiorenal disorders.

Post-myocardial infarction fibrosis: Pathophysiology, examination, and intervention

“…Other non-clinical trials have been reported in the recent years. For example, sliskiren is not only the first Food and Drug Administration-approved and orally active renin inhibitor to treat hypertension, but also regulates collagen metabolism and cardiac fibrosis in vivo and in vitro ( Kleinert, 1996 ; Zhi et al, 2013 ). Additionally, compound 21 is a non-peptide AT2R agonist with antifibrotic effect ( Wang et al, 2017 ).…”

Cardiac fibrosis: potential therapeutic targets

“…Direct renin inhibition may be a promising anti-fibrotic therapy since it attenuates the profibrotic effects of renin in addition to that of other effectors of the renin-angiotensin pathway 29 . Renin inhibitors interfere with the initial rate limiting step in the synthesis of AngII by binding directly to renin 30 . Aliskiren is the first orally active renin inhibitor approved by the FDA for the treatment of hypertension in adults 31 .…”