A Keegan1, M A Cotter, N E Cameron. 1. Department of Biomedical Sciences, University of Aberdeen, Aberdeen, Scotland, UK.
Abstract
BACKGROUND: The effects of streptozotocin-induced diabetes on nitric oxide (NO)-mediated relaxation of rat corpus cavernosum smooth muscle to neurogenic and endothelial stimulation was examined. The aim was to assess the effects of treatment with low doses of the antioxidant, alpha-lipoic acid, and the omega-6 essential fatty acid, gamma-linolenic acid, either separately or in combination. METHODS: Treatment was preventive from diabetes induction or corrective over 4 weeks after 4 weeks of untreated diabetes. Corpus cavernosum responses were examined in vitro. RESULTS: Neither diabetes nor treatment affected contractile responses to transmural electrical field stimulation of noradrenergic nerves. Stimulation of phenylephrine precontracted cavernosa in the presence of guanethidine and atropine caused relaxation via the nitrergic innervation. Maximum relaxation responses were 40% and 46% decreased after 4 and 8 weeks of diabetes, respectively. alpha-Lipoic acid, gamma-linolenic acid combination treatment fully prevented this deficit, and partially (52%) corrected the effect of 4 weeks of untreated diabetes. Neither alpha-lipoic acid nor gamma-linolenic components alone had significant effects, which suggests that there were synergistic interactions between the drugs. Both 4 and 8 weeks of untreated diabetes reduced maximum endothelium-dependent relaxation of phenylephrine precontracted cavernosa to acetylcholine by approximately 40%. While alpha-lipoic acid or gamma-linolenic acid were ineffective, joint treatment fully prevented and corrected this diabetic endothelial deficit. Neither diabetes nor treatment affected endothelium-independent relaxation to the NO donor, sodium nitroprusside. CONCLUSION: The data show that alpha-lipoic acid and gamma-linolenic acid interact synergistically to improve NO-mediated neurogenic and endothelium-dependent relaxation of corpus cavernosum in experimental diabetes. Copyright 2001 John Wiley & Sons, Ltd.
BACKGROUND: The effects of streptozotocin-induced diabetes on nitric oxide (NO)-mediated relaxation of rat corpus cavernosum smooth muscle to neurogenic and endothelial stimulation was examined. The aim was to assess the effects of treatment with low doses of the antioxidant, alpha-lipoic acid, and the omega-6 essential fatty acid, gamma-linolenic acid, either separately or in combination. METHODS: Treatment was preventive from diabetes induction or corrective over 4 weeks after 4 weeks of untreated diabetes. Corpus cavernosum responses were examined in vitro. RESULTS: Neither diabetes nor treatment affected contractile responses to transmural electrical field stimulation of noradrenergic nerves. Stimulation of phenylephrine precontracted cavernosa in the presence of guanethidine and atropine caused relaxation via the nitrergic innervation. Maximum relaxation responses were 40% and 46% decreased after 4 and 8 weeks of diabetes, respectively. alpha-Lipoic acid, gamma-linolenic acid combination treatment fully prevented this deficit, and partially (52%) corrected the effect of 4 weeks of untreated diabetes. Neither alpha-lipoic acid nor gamma-linolenic components alone had significant effects, which suggests that there were synergistic interactions between the drugs. Both 4 and 8 weeks of untreated diabetes reduced maximum endothelium-dependent relaxation of phenylephrine precontracted cavernosa to acetylcholine by approximately 40%. While alpha-lipoic acid or gamma-linolenic acid were ineffective, joint treatment fully prevented and corrected this diabetic endothelial deficit. Neither diabetes nor treatment affected endothelium-independent relaxation to the NO donor, sodium nitroprusside. CONCLUSION: The data show that alpha-lipoic acid and gamma-linolenic acid interact synergistically to improve NO-mediated neurogenic and endothelium-dependent relaxation of corpus cavernosum in experimental diabetes. Copyright 2001 John Wiley & Sons, Ltd.