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Effects of chronic type 5 phosphodiesterase inhibition on penile microvascular reactivity in hypertensive patients with erectile dysfunction: a randomized crossover placebo-controlled trial

Journal of Human Hypertension volume 35, pages 360–370 (2021)Cite this article

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Abstract

This randomized crossover and placebo-controlled trial evaluated the effects of daily use of sildenafil citrate (SIL, 1-month 50 mg twice daily) on penile and systemic endothelial microvascular function in hypertensive patients presenting with erectile dysfunction. The effects of SIL on arterial pressure were evaluated using ambulatory blood pressure monitoring (ABPM). Fifty patients diagnosed with primary arterial hypertension and erectile dysfunction (aged 57.4 ± 5.6 years), recruited in a tertiary public hospital, were treated with SIL (50 mg twice daily) or placebo (PLA) for two 30-day periods with a 30-day washout between them. Laser speckle contrast imaging coupled with acetylcholine skin iontophoresis was used to evaluate penile and systemic (forearm) cutaneous microvascular reactivity. SIL treatment increased penile basal microvascular flow (P = 0.002) and maximal endothelial-dependent peak response to skin iontophoresis of acetylcholine (ACh, P = 0.006). The area under the curve of microvascular vasodilation induced by ACh was also significantly increased (P = 0.02). Lastly, SIL treatment did not modify systemic microvascular reactivity. Twenty-four-hour ABPM (P = 0.0002) and daytime (P = 0.002) and nighttime (P = 0.001) mean diastolic blood pressure values were significantly reduced after SIL treatment. The scores of the Simplified International Index of Erectile Function (P < 0.0001) and the number of patients with positive responses to Sexual Encounter Profile question 3 (P < 0.0001) also increased after SIL treatment. Penile endothelium-dependent microvascular reactivity improved after continuous use of sildenafil in hypertensive patients with erectile dysfunction; the treatment also reduced blood pressure, suggesting that, in addition to improving erectile function, daily use of sildenafil could improve blood pressure control.

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Fig. 1: Effects of sildenafil on erectile function.
Fig. 2: Effects of increasing doses of acetylcholine iontophoresis on the cutaneous microvascular conductance of penile skin of the hypertensive patients (n = 50), expressed in arbitrary perfusion units (APU) divided by mean arterial pressure in mmHg, representing endothelium-dependent microvascular vasodilation before (PRE) and after (POST) chronic treatment with sildenafil (SIL) or placebo (PLA).
Fig. 3: Effects of the chronic treatment with sildenafil (SIL) or placebo (PLA) on single measurements of the penile microvascular reactivity of hypertensive patients with erectile dysfunction (n = 50).
Fig. 4: Effects of the chronic treatment with sildenafil (SIL) or placebo (PLA) on the blood pressure of hypertensive patients (n = 50).
Fig. 5: Effects of the chronic treatment with sildenafil (SIL) or placebo (PLA) on the blood pressure evaluated using ambulatory blood pressure monitoring (ABPM) of hypertensive patients (n = 50).

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  • 18 June 2020

    The original HTML version of this Article was updated shortly after publication in order to change all the figures from colour to black & white as per the authors’ request.

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Acknowledgements

The authors wish to thank Marcio Marinho Gonzalez for his excellent technical assistance.

Funding

CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico, ET grant # 305234/2017-0), FAPERJ (Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro, ET grant # E-26/202.822/2018).

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Authors and Affiliations

  1. National Institute of Cardiology, Ministry of Health, Rio de Janeiro, Brazil

    Valéria Verri, Alessandro R. Nascimento & Eduardo Tibirica

  2. State University of Rio de Janeiro, Rio de Janeiro, Brazil

    Andrea A. Brandao

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Contributions

VV and ET conceived and designed the study. VV and ET analyzed the data and interpreted the results of the experiments. ET drafted the manuscript. VV, AA and ET edited and revised the manuscript. All of the authors approved the final version of the manuscript.

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Correspondence to Eduardo Tibirica.

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Part of the present work was presented during the 26th European Meeting on Hypertension and Cardiovascular Protection (2016), during the European Society of Cardiology Congress (2017) and during the 29th European Meeting on Hypertension and Cardiovascular Protection (2019).

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Verri, V., Nascimento, A.R., Brandao, A.A. et al. Effects of chronic type 5 phosphodiesterase inhibition on penile microvascular reactivity in hypertensive patients with erectile dysfunction: a randomized crossover placebo-controlled trial. J Hum Hypertens 35, 360–370 (2021). https://doi.org/10.1038/s41371-020-0343-3

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