The role of apoptosis and caspase inhibitor on experimental low-flow priapism induced endothelial injury in rats

Priapism is a persistent unwanted erection that is not associated with sexual desire or sexual stimulation. Low-flow or ischemic priapism is the most common form of priapism. Apoptosis plays an important role in secondary erectile dysfunction due to inappropriately treated ischemic priapism. In this study, the role of apoptosis in the physiopathology of low-flow priapism and the effects of zVAD-fmk, an inhibitor of apoptosis, on erectile dysfunction due to low-flow priapism was studied on a rat model. Twenty-four adult Sprague-Dawley rats were equally assigned into 4 groups. In all rats but those in the control group erections were obtained by vacuum method and maintained for 4 hours to develop priapism. Before the development of priapism DMSO (1 mL/kg i.p.), zVAD-fmk (1 mg/kg i.p.), %0.9 NaCl (1 mL/kg i.p.) were administered to the corresponding groups. After 14 days following this procedure penile en bloc excision was performed and cavernous tissues were investigated pharmacologically and histopathologically. Isometric contraction experiments revealed no difference between groups. In isometric relaxation experiments however, the cavernosal tissues obtained from priapism-developed rats relaxed less than those obtained from the control group. Cavernosal tissues obtained from zVAD-fmk pretreated rats showed similar relaxation patterns as in the control groups. Also cavernosal tissues obtained from DMSO pretreated rats revealed similar isometric relaxation responses with the controls. In histopathological investigations, a mean of 60.3% apoptosis was determined in the cavernosal tissue obtained from priapism-developed rats, the average values for apoptosis determined in the cavernosal tissues obtained from zVAD-fmk- and DMSO- pretreated rats were 27% and 30.8%, respectively. A mean of 31.8% apoptosis was determined in the cavernosal tissues obtained from the control group. These findings denote that ischemic priapism causes permanent damage on erectile functions, particularly on relaxation of the cavernosal tissue. Inhibition of priapism induced apoptosis with zVAD-fmk seems promising on preserving erectile functions.