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Novel therapeutic targets for hypertension

Nature Reviews Cardiology volume 7, pages 431–441 (2010)Cite this article

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Abstract

Despite the existence of established, effective therapies for hypertension, new methods of blood pressure and cardiovascular risk reduction are still needed. Novel approaches are targeted towards treating resistant hypertension, improving blood-pressure control, and achieving further risk reduction beyond blood-pressure lowering. Modulation of the renin–angiotensin–aldosterone system (RAAS) provides the rationale for current antihypertensive therapies, including the relatively new agents eplerenone and aliskiren. Novel targets for antihypertensive therapy are also likely to be RAAS-related. The stimulation of angiotensin II type 2 receptors, or supplementation with renalase, could counteract the effects of angiotensin II type 1 receptor stimulation or catecholamine release. Combined angiotensin-converting-enzyme and neutral endopeptidase blockade decreases blood pressure, but is associated with a high incidence of angioedema. Aldosterone synthase inhibitors might improve tolerability in aldosterone antagonism. A (pro)renin-receptor blocker could prevent the deleterious angiotensin-independent actions of renin that are not inhibited by aliskiren. Finally, new minimally invasive surgical procedures have revived the concept of renal denervation, and could be a therapeutic option for patients with resistant hypertension. All of these strategies are exciting prospects, but which of them will prove valuable in clinical setting remains to be discovered.

Key Points

  • Most current effective agents for blood-pressure control, and possible future antihypertensives, are related to inhibition of the renin–angiotensin–aldosterone system

  • The unmet needs for antihypertensive therapy include the treatment of resistant hypertension, improving blood-pressure control, and achieving further cardiovascular risk reduction

  • The efficacy of newly approved medications for high blood pressure (aldosterone receptor blockers and renin inhibitors) still needs to be confirmed, particularly in reducing mortality

  • Novel targets for antihypertensive therapy could include the angiotensin II type 2 receptor, neutral endopeptidase, aldosterone synthase, renalase, the (pro)renin receptor, and renal innervations

  • The development of hybrid molecules and fixed-dose combinations of existing therapies are likely to prevail in future hypertension research

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Figure 1: The renin–angiotensin–aldosterone system: vasoactive balance and targets for antihypertensive therapy.

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Acknowledgements

L. Paulis was supported by the Marie Curie Intra-European Fellowship (2009–237834) within the 7th European Community Framework Program.

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  1. Center for Cardiovascular Research, Charité-Universitätsmedizin, Hessische Strasse 3–4, 10115, Berlin, Germany

    Ludovit Paulis & Thomas Unger

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  1. Ludovit Paulis
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  2. Thomas Unger
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Correspondence to Thomas Unger.

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Competing interests

T. Unger has received research support from Vicore Pharma. L. Paulis declares no competing interests.

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Paulis, L., Unger, T. Novel therapeutic targets for hypertension. Nat Rev Cardiol 7, 431–441 (2010). https://doi.org/10.1038/nrcardio.2010.85

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