[Renin, prorenin, and the direct renin inhibitor aliskiren].
The renin-angiotensin system plays an important role in various physiological and pathophysiological regulatory mechanisms. Within the past few years, the classical concept of a linear enzymatic cascade has experienced substantial changes. A parallel counterregulatory axis has been identified which involves the angiotensin converting enzyme homologue ACE2, angiotensin (1-7), and receptors Mas. The research in prorenin and its non-proteolytic activation has greatly advanced after the discovery of cellular receptors (P)RR; binding of renin or prorenin to these receptors not only facilitates angiotensin generation, but at the same time activates specific signal transduction pathways. The long-term search for clinically useful direct renin inhibitors has recently succeeded with the new antihypertensive drug aliskiren. While beneficial effects of aliskiren on some markers of cardiovascular and renal diseases have been proved in large clinical studies, important questions remain to be solved.
Slabý
Adolf
A
Univerzita Karlova v Praze, 1. lékarská fakulta, IV. Interní klinika VFN. adolf.slaby@vfn.cz
Zák
Ales
A
D000577:Amides / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005650:Fumarates / Q000494:pharmacology*; D006801:Humans; D011956:Receptors, Cell Surface / Q000502:physiology; D012083:Renin / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology; D025262:Vacuolar Proton-Translocating ATPases / Q000502:physiology; D000092502:Renin Inhibitors; D000093342:Prorenin Receptor
D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D011956:Receptors, Cell Surface; D012083:Renin; D025262:Vacuolar Proton-Translocating ATPases; D000092502:Renin Inhibitors; C458319:ATP6AP2 protein, human; D000093342:Prorenin Receptor; C446481:aliskiren