Cimetidine-induced vascular cell apoptosis impairs testicular microvasculature in adult rats
Flávia L. Beltrame1, Caroline T. Yamauti2, Breno H. Caneguim1, Paulo S. Cerri2, Sandra M. Miraglia1 and Estela Sasso-Cerri2
1Department of Morphology and Genetics, Federal University of São Paulo (UNIFESP), São Paulo/SP, Brazil and 2Department of Morphology, Laboratory of Histology and Embryology, Dental School – São Paulo State University (UNESP), Araraquara/SP, Brazil
Offprint requests to: Dra. Estela Sasso-Cerri, Faculdade de Odontologia de Araraquara (UNESP/FOAr), Departamento de Morfologia, Laboratorio de Histologia e Embriologia, Rua Humaitá 1680, 14801-903, Araraquara/SP, Brazil. e-mail: esasso@foar.unesp.br
Summary. Cimetidine, an H2 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 H2 receptors and/or androgen receptors in the vascular cells may be responsible for the impairment of the testicular microvasculature. Histol Histopathol 27, 1343-1351 (2012)
Key words: H2 receptor antagonist, Microvascular density, Vascular atrophy, Cell death, Smooth muscle cell
DOI: 10.14670/HH-27.1343