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Heme-induced corpus cavernosum relaxation and its implications for priapism in sickle cell disease: a mechanistic insight.
Pereira, Dalila Andrade; Pereira, Danillo Andrade; Silveira, Tammyris Helena Rebecchi; Calmasini, Fabiano Beraldi; Burnett, Arthur L; Costa, Fernando Ferreira; Silva, Fábio Henrique.
Afiliación
  • Pereira DA; Laboratory of Pharmacology, São Francisco University Medical School, Bragança Paulista, São Paulo, SP, Brazil.
  • Pereira DA; Laboratory of Pharmacology, São Francisco University Medical School, Bragança Paulista, São Paulo, SP, Brazil.
  • Silveira THR; Laboratory of Pharmacology, São Francisco University Medical School, Bragança Paulista, São Paulo, SP, Brazil.
  • Calmasini FB; Department of Pharmacology, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, SP, Brazil.
  • Burnett AL; The James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
  • Costa FF; Hematology and Hemotherapy Center, University of Campinas, Campinas, São Paulo, SP, Brazil.
  • Silva FH; Laboratory of Pharmacology, São Francisco University Medical School, Bragança Paulista, São Paulo, SP, Brazil.
Andrology ; 2024 Jan 17.
Article en En | MEDLINE | ID: mdl-38231174
ABSTRACT

BACKGROUND:

Patients with sickle cell disease (SCD) experience intravascular hemolysis, leading to elevated plasma heme levels. This phenomenon has been associated with increased priapism in men with SCD. The heme group can be metabolized by heme oxygenase (HO), generating carbon monoxide (CO), which is known to promote smooth muscle relaxation via soluble guanylyl cyclase (sGC)-cyclic guanosine monophosphate (cGMP). However, the effects of heme on the relaxation responses of corpus cavernosum (CC) have not been investigated.

OBJECTIVES:

To evaluate the functional and biochemical effects of the heme group on mouse CC smooth muscle in vitro. MATERIALS AND

METHODS:

Male C57BL/6 mice were used. CC tissues were mounted in organ baths. Measurement of cGMP in mice CC was evaluated.

RESULTS:

The cumulative addition of heme concentrations promoted the relaxation of CC. HO inhibitor (1J, 100 µM) or sGC inhibitor (ODQ, 10 µM) blocked the relaxing effect of the heme group. Pre-incubation of CC with heme (100 µM) enhanced relaxation induced by acetylcholine, sodium nitroprusside, and nitrergic relaxation (electrical field stimulation), which was abolished by 1J or ODQ. The heme group increased the cGMP production in CC, which was abolished by 1J or ODQ. cGMP levels were significantly higher in CC treated with heme, and pre-incubation with compound 1J or ODQ abolished the effect of heme in raising cGMP levels. DISCUSSION AND

CONCLUSION:

The HO-CO-sGC-cGMP pathway appears to play a crucial role in promoting CC relaxation. Our study provides novel insight into the role of group heme in CC relaxation and its potential contribution to priapism in SCD. Heme may serve as a pharmacological target for new therapies to prevent priapism.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Andrology Año: 2024 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Andrology Año: 2024 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido