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.
Krum
Henry
H
NHMRC Centre of Clinical Excellence in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University/Alfred Hospital,Central and Eastern Clinical School, Melbourne, Victoria 3004, Australia. henry.krum@med.monash.edu.au
Gilbert
Richard E
RE
D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D000085962:Angiotensin-Converting Enzyme 2; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016373:DNA, Antisense / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D015260:Neprilysin / Q000037:antagonists & inhibitors; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011480:Protease Inhibitors / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D014612:Vaccines / Q000627:therapeutic use; D000092502:Renin Inhibitors
D000804:Angiotensin II; D047228:Angiotensin II Type 1 Receptor Blockers; D000085962:Angiotensin-Converting Enzyme 2; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D016373:DNA, Antisense; D000451:Mineralocorticoid Receptor Antagonists; D015260:Neprilysin; D007703:Peptidyl-Dipeptidase A; D011480:Protease Inhibitors; D047428:Protein Kinase Inhibitors; D044140:Receptor, Angiotensin, Type 1; D017978:Receptors, Growth Factor; D014612:Vaccines; D000092502:Renin Inhibitors; C000705307:ACE2 protein, human