Does endogenous testosterone mediate the lower preconditioning threshold in males?

Background Preconditioning is injury-induced protection from subsequent insult. Recent data indicates that males have lower preconditioning thresholds compared to females. Therefore, we hypothesized that testosterone may mediate the lower preconditioning threshold observed in males. Materials and methods Adult normal and castrated male Sprague-Dawley rats (n = 4–5) were given intraperitoneal (i.p.) injections of 125 or 500 μg/kg Salmonella typhimurium lipopolysaccharide (ETX) or 0.4 ml normal saline (NS). Another i.p. injection of 500 μg/kg ETX (injury dose) was given 24 h later. After 6 h, myocardial function was evaluated via the Langendorff perfusion model. Shams received only NS, while non-preconditioned rats (PC-) received NS followed by the 500 μg/kg ETX injury dose. Preconditioned rats received injections of 125 μg/kg ETX (PC +125) or 500 μg/kg ETX (PC +500), followed by the 500 μg/kg ETX injury dose. Results Normal PC +125 and PC +500 males were preconditioned and maintained cardiac function similar to shams (P > 0.05). Castrated PC +125 and PC +500 males were also preconditioned and maintained cardiac function similar to castrated shams (P > 0.05). Conversely, both normal and castrated PC-males showed significantly decreased cardiac function compared to shams (P Conclusions Endogenous testosterone does not mediate the lower preconditioning threshold in males.