Korkach Y. Synthesis of nitric oxide in cardiovascular system at ageing and diabetes mellitus and pathways of its correction

In the aorta, heart and heart's mitochondria of rats it was studied the activity of arginase, nitrate reductase and the two NO synthase (NOS) isoforms - inducible (iNOS) and constitutive (cNOS). This activities was tested at the different oxidative stress levels in young (6 month), aging (21 month) and diabetic rats. Aging rats demonstrated endothelial dysfunction depend on both high activity of ROS and nitric oxide synthesis by iNOS and nitrate reductase, as well as by low activity of constitutive NO synthesis in aorta, heart and heart's mitochondria. Angiotensin-converting enzyme inhibitor enalaprile administration (20 mg/kg, 60 days) up-regalate cNOS activity and down-regulate iNOS, nitrate reductase activity and ROS generation in aging rats. Low doses ecdysterone oral administration (10 mkg/100g, 2 weeks) normalized NO synthesis by iNOS, cNOS and NADHP- dependent nitrate reductase, as well as L-arginine degradation by arginase in heart's mitochondria of aging rats. Chronic hyperglycemia (60 days)that are developed after streptozotocine - administration (50mg/100g) in rats was up regulates oxidative and nitrosative stresses as well as ROS generation and nitric oxide de novo and salvage synthesis disregulation in aorta, heart and heart's mitochondria. This potent hypoglycemic effect of ecdysterone is depend on inhibition of nonconstitutive NO synthesis by iNOS and nitrate reductase as well as inhibition of L-arginine degradation by arginase result in up-regulation of constitutive NO synthesis in heart and aorta in rats.