Novel therapies blocking the renin–angiotensin–aldosterone system in the management of hypertension and related disorders

Although significant advances have been made in the therapeutic blockade of the renin-angiotensin-aldosterone system (RAAS) using angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers and non-selective aldosterone receptor antagonists, there is a clear need for both additional blocking strategies and enhancements of current therapeutic approaches. Vasopeptidase inhibition may still find a role despite the small incremental value of this approach and the obvious issue of kinin-mediated adverse effects still to be fully addressed. Blockade of the RAAS upstream using renin inhibitors as well as the greater selectivity of aldosterone blockade using selective aldosterone blockers such as eplerenone are also novel approaches. Not yet in clinical use but certainly an attractive therapeutic target is angiotensin II growth factor receptor transactivation, with selective inhibitors having been developed for various specific kinase pathways. Finally, ACE2 augmentation, antisense gene strategies, and vaccination against the renin-angiotensin system should still be considered experimental, but have significant appeal as additional approaches to the blockade of this system.