Cimetidine-induced vascular cell apoptosis impairs testicular microvasculature in adult rats

Cimetidine-induced vascular cell apoptosis impairs testicular microvasculature in adult rats

Author Beltrame, Flavia Luciana Autor UNIFESP Google Scholar
Yamauti, Caroline T. Google Scholar
Caneguim, Breno Henrique Autor UNIFESP Google Scholar
Cerri, Paulo Sergio Autor UNIFESP Google Scholar
Miraglia, Sandra Maria Autor UNIFESP Google Scholar
Sasso-Cerri, Estela Autor UNIFESP Google Scholar
Institution Sao Paulo State Univ UNESP
Universidade Federal de São Paulo (UNIFESP)
Abstract Cimetidine, an H-2 receptor antagonist used for treatment of gastric ulcers, exerts antiandrogenic and antiangiogenic effects. In the testes cimetidine impairs spermatogenesis, Sertoli cells and peritubular tissue, inducing apoptosis in the myoid cells. Regarding the importance of histamine and androgens for vascular maintenance, the effect of cimetidine on the structural integrity of the testicular vasculature was evaluated. Adult male rats received cimetidine (CMTG) and saline (CG) for 50 days. The testes were fixed in buffered 4% formaldehyde and embedded in historesin and paraffin. In the PAS-stained sections, the microvascular density (MVD) and the vascular luminal area (VLA) were obtained. TUNEL method was performed for detection of cell death. Testicular fragments embedded in Araldite were analyzed under transmission electron microscopy. A significant decrease in the MVD and VLA and a high number of collapsed blood vessel profiles were observed in CMTG. Endothelial cells and vascular muscle cells were TUNEL-positive and showed ultrastructural features of apoptosis. These results indicate that cimetidine induces apoptosis in vascular cells, leading to testicular vascular atrophy. A possible antagonist effect of cimetidine on the H-2 receptors and/or androgen receptors in the vascular cells may be responsible for the impairment of the testicular microvasculature.
Keywords H-2 receptor antagonist
Microvascular density
Vascular atrophy
Cell death
Smooth muscle cell
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 2006/50324-3
FAPESP: 2006/54776-6
FAPESP: 2007/53207-0
FAPESP: 2010/02409-5
Date 2012-10-01
Published in Histology And Histopathology. Murcia: F Hernandez, v. 27, n. 10, p. 1343-1351, 2012.
ISSN 0213-3911 (Sherpa/Romeo, impact factor)
Publisher F Hernandez
Extent 1343-1351
Access rights Closed access
Type Article
Web of Science ID WOS:000308583700011

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