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Early manifestation of aging-related vascular dysfunction in human penile vasculature—A potential explanation for the role of erectile dysfunction as a harbinger of systemic vascular disease

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Abstract

Advanced age is related to functional alterations of human vasculature, but erectile dysfunction precedes systemic manifestations of vascular disease. The current study aimed to simultaneously evaluate the influence of aging on vascular function (relaxation and contraction responses) in systemic human vascular territories: aorta (HA) and resistance mesenteric arteries (HMA) and human corpus cavernosum (HCC) and penile resistance arteries (HPRA). Associations of oxidative stress and inflammation circulating biomarkers with age and functional responses were also determined. Vascular specimens were obtained from 76 organ donors (age range 18–87). Four age-groups were established: < 40, 40–55, 56–65 and > 65 years old. Increasing age was associated with a decline in endothelium-dependent relaxation induced by BK in HMA (r = -0.597, p = 0.0001), or by ACh in HCC (r = -0.505, p = 0.0022), and HPRA (r = -0.601, p = 0.0012). Significant impairment was detected at > 65 years old in HMA but earlier in penile vasculature (> 55 years old). Age-related reduction to H2O2-vasodilatory response started before in HCC (56–65 years old) than in HA (> 65 years old). In contrast to relaxation responses, aging-related hypercontractility to adrenergic stimulation was homogeneous: contractions significantly increased in subjects > 55 years old in all tested vessels. Although not significantly age related, circulating levels of ADMA (r = -0.681, p = 0.0052) and TNF-α (r = -0.537, p = 0.0385) were negatively correlated with endothelial vasodilation in HMA but not in HCC or HPRA. Penile vasculature exhibits an early impairment of endothelium-dependent and H2O2-induced vasodilations when compared to mesenteric microcirculation and aorta. Therefore, functional susceptibility of penile vasculature to the aging process may account for anticipation of erectile dysfunction to systemic manifestations of vascular disease.

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Acknowledgements

We appreciate the altruistic contribution of donors and their relatives as well as all the personnel involved in organ donation and transplantation teams at Hospital Universitario Doce de Octubre, Madrid, Spain, and at the Hospital Geral de Santo Antonio, Porto, Portugal, for making this study possible.

Funding

The research leading to these results has received funding from the Ministry of Economy and Competitiveness and co-financed by FEDER funds (Instituto de Salud Carlos III, PI15/00674, PI15/01160, PI15/01969, PI20/00977 and CIBERFES (CB16/10/00464), Spanish Government.

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  1. Mariam El Assar and Javier Angulo contributed equally to this work.

Authors and Affiliations

  1. Fundación de Investigación Biomédica, del Hospital Universitario de Getafe, Getafe, Spain

    Mariam El Assar, Alberto Sánchez-Ferrer & Leocadio Rodríguez-Mañas

  2. Centro de Investigación Biomédica en Red de Fragilidad Y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain

    Mariam El Assar, Javier Angulo & Leocadio Rodríguez-Mañas

  3. Servicio de Histología-Investigación, Unidad de Investigación Traslacional en Cardiología (IRYCIS-UFV), Hospital Universitario Ramón Y Cajal, Madrid, Spain

    Javier Angulo, Alejandro Sevilleja-Ortiz & Argentina Fernández

  4. Department of Urology, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital, 12 de Octubre (imas12), Madrid, Spain

    Esther García-Rojo, Borja García-Gómez & Javier Romero-Otero

  5. Serviço de Urologia, Hospital Geral Santo Antonio, Porto, Portugal

    José M. La Fuente

  6. Division of Geriatric Medicine, Servicio de Geriatría, Hospital Universitario de Getafe, Ctra de Toledo km 12, 500, 8905, Getafe, Spain

    Leocadio Rodríguez-Mañas

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Contributions

MEA, JA, JRO and LRM participated in conceptualization and design of the study; MEA, JA, EGR, ASO, BGG, AF, ASF, JMLF and LRM performed data acquisition analysis and interpretation; MEA, JA, and LRM wrote the original draft of the manuscript; all authors reviewed, edited, and approved the final version of the manuscript.

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Correspondence to Leocadio Rodríguez-Mañas.

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The study protocols were approved by the Ethics Committees of the Hospital Universitario de Getafe, Getafe, Spain (Ethics Approval procedure A06/15, April 30th, 2015), the Hospital Universitario Doce de Octubre, Madrid, Spain (Ethics Approval procedure 16/045, February 25th, 2016), the Hospital Universitario Ramón y Cajal, Madrid, Spain (Ethics Approval procedure 363–15, March 3rd, 2016), and the Hospital Geral de Santo Antonio, Porto, Portugal (210–15 (174-DEFI/156-CES, May 27th, 2016).

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Assar, M.E., Angulo, J., García-Rojo, E. et al. Early manifestation of aging-related vascular dysfunction in human penile vasculature—A potential explanation for the role of erectile dysfunction as a harbinger of systemic vascular disease. GeroScience 44, 485–501 (2022). https://doi.org/10.1007/s11357-021-00507-x

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