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Understanding and targeting the Rho kinase pathway in erectile dysfunction

Nature Reviews Urology volume 11, pages 622–628 (2014)Cite this article

Subjects

Key Points

  • RhoA–ROCK signalling is important for erectile homeostasis, and acts by potentiating Ca2+-dependent contraction to maintain penile flaccidity

  • Dysregulation of the RhoA–ROCK pathway has an important role in the aetiology of erectile dysfunction

  • RhoA–ROCK inhibition improves erectile dysfunction, even for hard-to-treat causes, such as diabetes

  • Several RhoA–ROCK inhibitors are being investigated in clinical trials and could provide new treatment options

Abstract

Erectile dysfunction (ED) is a common disorder that affects a quarter of US men, and has many causes, including endothelial impairment, low testosterone levels, prior surgical manipulation, and/or psychogenic components. Penile erection is a complex process requiring neurally mediated relaxation of arteriolar smooth muscle and engorgement of cavernosal tissues, mediated by nitric oxide (NO). Current medical therapies for ED largely seek to maximize endogenous NO signalling. Certain aetiologies, including diabetes, are difficult to treat with current modalities, emphasizing the need for new molecular targets. Research has demonstrated the importance of RhoA–Rho-associated protein kinase (ROCK) signalling in maintaining a flaccid penile state, and inhibition of RhoA–ROCK signalling potentiates smooth-muscle relaxation in an NO-independent manner. The mechanisms and effects of RhoA–ROCK signalling and inhibition suggest that the RhoA–ROCK pathway could prove to be a new therapeutic target for the treatment of ED.

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Figure 1: Pathways of contraction and relaxation in cavernosal smooth-muscle cells.

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Authors and Affiliations

  1. James Buchanan Brady Urological Institute, The Johns Hopkins School of Medicine, 1800 Orleans Street/Marburg 134, Baltimore, 21287, MD, USA

    Nikolai A. Sopko, Johanna L. Hannan & Trinity J. Bivalacqua

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  1. Nikolai A. Sopko
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  2. Johanna L. Hannan
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Correspondence to Nikolai A. Sopko.

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Sopko, N., Hannan, J. & Bivalacqua, T. Understanding and targeting the Rho kinase pathway in erectile dysfunction. Nat Rev Urol 11, 622–628 (2014). https://doi.org/10.1038/nrurol.2014.278

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