The increase in renin during renin inhibition: does it result in harmful effects by the (pro)renin receptor?

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Renin inhibitors, similar to all renin-angiotensin system (RAS) blockers, increase the plasma concentration of renin because they attenuate the negative feedback effect of angiotensin (Ang) II on renin release. The increase in renin has been suggested to be higher than that during other types of RAS blockade. This could potentially limit the effectiveness of renin inhibition, either because Ang II generation might occur again ('Ang II escape'), possibly even at the levels above baseline, as has been described before for angiotensin-converting enzyme inhibitors, or because high levels of renin will stimulate the recently discovered (pro) renin receptor, and thus induce effects in an Ang-independent manner. This review shows first that the cause(s) of the renin increase during treatment with the renin inhibitor aliskiren is the consequence of a combination of factors, including an assay artifact, allowing the detection of prorenin as renin, and a change in renin half-life. When correcting for these phenomena the increase is unlikely to be as excessive as originally thought. The review then critically describes the consequence(s) of such a increase, concluding (i) that an Ang II escape is highly unlikely, given the [aliskiren]/[renin] stoichiometry, and (ii) that renin and prorenin downregulate their receptor (similar to many agonists). On the basis of the latter, one could even speculate that this will be more substantial when the renin and prorenin levels are higher. Thus, from this point of view the larger increase in renin during renin inhibition will cause a stronger reduction in (pro) renin receptor expression, and a greater suppression of (pro) renin receptor-mediated effects than other renin-Ang blockers. Hypertension Research (2010) 33, 4-10; doi: 10.1038/hr.2009.186; published online 6 November 2009
Original languageUndefined/Unknown
Pages (from-to)4-10
Number of pages7
JournalHypertension Research
Issue number1
Publication statusPublished - 2010

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  • EMC COEUR-09

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