L-cysteine/hydrogen sulfide pathway induces cGMP-dependent relaxation of corpus cavernosum and penile arteries from patients with erectile dysfunction and improves arterial vasodilation induced by PDE5 inhibition.

Autor: La Fuente JM; Serviço de Urologia, Hospital Santo Antonio, Porto, Portugal., Fernández A; Servicio de Histología-Investigación, Unidad de Investigación Traslacional en Cardiología (UFV-IRYCIS), Hospital Universitario Ramón y Cajal, Madrid, Spain., Pepe-Cardoso AJ; Serviço de Urologia, Hospital Fernando da Fonseca, Amadora-Sintra, Portugal., Martínez-Salamanca JI; Servicio de Urología, Hospital Universitario Puerta de Hierro, Majadahonda, Spain., Louro N; Serviço de Urologia, Hospital Santo Antonio, Porto, Portugal., Angulo J; Servicio de Histología-Investigación, Unidad de Investigación Traslacional en Cardiología (UFV-IRYCIS), Hospital Universitario Ramón y Cajal, Madrid, Spain. Electronic address: javier.angulo@hrc.es.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2019 Nov 15; Vol. 863, pp. 172675. Date of Electronic Publication: 2019 Sep 19.
DOI: 10.1016/j.ejphar.2019.172675
Abstrakt: The aim was to evaluate and characterize H 2 S-induced relaxation of human corpus cavernosum (HCC) and penile resistance arteries (HPRA) from patients with erectile dysfunction (ED). HCC and HPRA were obtained from men with ED at the time of penile prosthesis insertion. H 2 S-mediated relaxations were evaluated by exposing these tissues to the stable analogue, NaHS, and to the precursor of H 2 S, L-cysteine (CYS). The effects of NaHS and CYS were also evaluated on cGMP accumulation in HCC and on acetylcholine- and sildenafil-mediated relaxations in HCC and HPRA. NaHS consistently relaxed HPRA and HCC and more potently than human prostate and bladder. NaHS-induced relaxations in HCC and HPRA were unaffected by the ATP-sensitive K + -channel blocker, glibenclamide or the NO synthase inhibitor, L-NAME, slightly reduced by the Ca 2+ -activated K + -channel blocker, tetraethylammonium, and markedly inhibited by the soluble guanylyl cyclase inhibitor, ODQ. NaHS caused a cGMP increase in HCC that was inhibited by ODQ. CYS produced relaxations of HCC and HPRA that were sensitive to ODQ and to inhibition of the H 2 S synthesizing enzymes, cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS). CYS also increased cGMP in HCC. In contrast to NaHS, CYS-induced relaxations were prevented by endothelium removal in HPRA. Only in HPRA, treatment with CYS (30 μM) potentiated acetylcholine- and sildenafil-induced relaxations. This effect was prevented by CSE/CBS inhibition and by removing the endothelium. Exogenous and endogenous H 2 S relaxes HCC and HPRA from ED patients through cGMP accumulation and potentiates vasodilatory capacity of PDE5 inhibition, supporting the therapeutic potential of modulating H 2 S pathway.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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