Study of interaction between nitric oxide and ACE activity in STZ-induced diabetic rats: role of insulin.
The precise mechanisms of vascular diseases in patients with insulin-dependent diabetes mellitus (IDDM) are not clearly understood. There are evidences of alteration in mechanisms involved in regulating vascular tone including increased ACE activity and decreased NO production in STZ diabetic rats. Insulin treatment may reverse these changes by an unknown mechanism. This study sought to examine the interaction of ACE activity and NO and how insulin treatment affected these mechanisms. Four groups of eight male Sprauge-Dawely rats including control (C) and three diabetic groups (D, IT and LIT) were used in this study. Diabetes induced by injection of 60 mg kg(-1) STZ i.p. After induction of diabetes IT group treated with insulin (10 units kg(-1) daily s.c.) for 4 weeks. LIT group received the same amount of insulin and N(omega)-nitro-l-arginine methyl ester (L-NAME; 20 mg kg(-1) i.p.) for the same period. The D group was diabetic control that treated with saline. ACE activity was determined by HPLC method. At the end of study in D group ACE activity was increased in aorta, heart, lung and serum but Serum NO(x) (nitrate and nitrite) concentration decreased compared to C group. These values were reversed to normal by insulin treatment in IT group. In LIT group the ACE activity remained elevated only in aorta and heart while the serum NO(x) was lower than control group. It is concluded that ACE reducing activity of insulin in aorta and heart of STZ-induced diabetic rats may be mediated by elevation of NO by insulin treatment.
Sharifi
Ali M
AM
Department of Pharmacology and Cellular and Molecular Research Center, School of Medicine, Iran University of Medical Sciences, P.O. Box 14155-6183, Tehran, Iran. sharifal@yahoo.com
Mousavi
Seyed Hadi
SH
Larijani
Bagher
B
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D007703:Peptidyl-Dipeptidase A / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D007328:Insulin; D009569:Nitric Oxide; D007703:Peptidyl-Dipeptidase A