Abstract
Abstract Introduction Erectile dysfunction is associated with increased contraction and decreased relaxation of the corpus cavernosum (CC). Excessive reactive oxygen species produced by mitochondria play a key role in aging- and diabetes-induced erectile dysfunction. Erectile dysfunction is associated with increased contraction and decreased relaxation of the corpus cavernosum. Mitochondrial deterioration is part of normal physiological aging, and it plays a role in the pathogenesis of age-related disorders by producing reactive oxygen species (ROS). It is also known that excessive ROS produced by mitochondria plays a key role in aging- and diabetes-induced erectile dysfunction. Objective We aimed to test the hypothesis that in vitro inhibition of mitochondrial oxidative stress improves the reactivity of the CC. Methods To test this hypothesis, the CC of young (3 to 4-month-old) and old (10 to 14-month-old) male lean and diabetic (dbdb-/-) mice were mounted in myographs. Concentration-response curves to acetylcholine (ACh 1 nM – 30 uM) and relaxation induced by electrical field stimulation (EFS – 1, 2, 4, 8 and 16 Hz) were obtained. All curves were repeated after 30 minutes of incubation with the antioxidant Mito-Q (100 nM). Results Results: Relaxation to ACh was significantly reduced in the CC of diabetic mice (Lean: 87 ± 8% vs dbdb-/-: 60 ± 6%). Similarly, aged lean mice presented impaired relaxation to ACh (Lean old: 54 ± 6%) while old diabetic mice displayed a further decrease in the relaxing response to ACh (35 ± 6%). After 30 minutes of incubation with Mito-Q, the relaxation produced by ACh was improved in the CC of the aged lean mice (62 ± 3%) and aged diabetic mice (44 ± 1%). Relaxing responses to EFS were significantly decreased in obese and aged mice compared to the lean young animals. However, no improvement in the relaxing response to EFS was seen after incubation with Mito-Q. Conclusions Impairment in the endothelium-dependent relaxation of the CC induced by aging and diabetes is associated with increased production of mitochondrial reactive oxygen species. The use of the mitochondrial-targeted antioxidant Mito-Q improved at least in part the relaxation of the CC in both aged and diabetic mice. Disclosure No
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