Physiological testosterone attenuates profibrotic activities of rat cardiac fibroblasts through modulation of nitric oxide and calcium homeostasis

Testosterone deficiency is associated with poor prognosis among patients chronic heart failure (HF). Physiological testosterone improves the exercise capacity of HF. In this study, we evaluated whether treatment physiological contributes to anti-fibrogenesis by modifying calcium homeostasis in cardiac fibroblasts and studied underlying mechanisms. Nitric oxide (NO) analyses, (Ca2+) fluorescence, Western blotting were performed primary isolated rat or without (control cells) (10, 100, 1,000 nmol/L) for 48 hours. (10 increased NO production phosphorylation at inhibitory site inositol trisphosphate (IP3) receptor, thereby reducing Ca2+ entry, phosphorylated Ca2+/calmodulin-dependent protein kinase II (CaMKII) expression, type I III pro-collagen production. Non-physiological testosterone-treated exhibited similar collagen capabilities as compared control (testosterone deficient) fibroblasts. These effects blocked co-treatment inhibitor (L-NG-nitro arginine methyl ester [L-NAME], 100 μmol/L). presence IP3 receptor (2-aminoethyl diphenylborinate [2-APB], 50 μmol/L), testosterone-deficient CaMKII expression. When treated 2-APB (KN93, 10 I, conclusion, activates production, attenuates receptor/Ca2+ entry/CaMKII signaling pathway, inhibiting capability