vasoactive-intestinal-peptide and pimagedine

The aim of this study was to investigate the ability of aminoguanidine (AG) to prevent diabetes-induced changes in nitric oxide synthase- (nNOS), vasoactive intestinal polypeptide- (VIP) and noradrenaline- (NA) containing nerves of the rat ileum using immunohistochemical and biochemical techniques. Diabetes was induced in adult male Wistar rats by a single intraperitoneal injection of streptozotocin (65 mg/kg). AG was administered in the drinking water to control (1.8 g/l) and diabetic (0.9 g/l) rats over a period of 8 weeks. Diabetes caused a significant increase in the thickness of nNOS-containing nerve fibres (p<0.001) in the circular muscle, in nNOS activity (p<0.05) and in the size distribution of nNOS-containing myenteric neurons (p<0.001). The thickness of VIP-containing nerve fibres was significantly greater (p<0.01) and there was a significant increase in varicosity size (p<0.01) and proportion of VIP-positive myenteric neurons (p<0.01) in diabetes. NA levels were significantly reduced (p<0.01) and the size of varicosities containing tyrosine hydroxylase (TH) was significantly increased (p<0.001) in diabetes. AG treatment completely or partially prevented the diabetes-induced increase in nNOS activity, in VIP-containing varicosity size, and in fibre width of both VIP- and nNOS-containing fibres in the circular muscle but had no effect on the diabetes-induced increase in nNOS-containing neuronal size or proportion of VIP-containing myenteric neurons. In contrast to VIP, AG treatment had no effect on the increase in TH-containing varicosity size in diabetes and also failed to prevent the decrease in NA levels induced by diabetes. These results indicate that AG treatment for neuropathy is not equally effective for all autonomic nerves supplying the ileum and that diabetes-induced changes in NA-containing nerves are particularly difficult to treat.

Topics: Animals; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Enzyme Inhibitors; Guanidines; Ileum; Immunohistochemistry; Male; Myenteric Plexus; Nerve Degeneration; Neurons; Nitric Oxide Synthase Type I; Norepinephrine; Rats; Rats, Wistar; Vasoactive Intestinal Peptide

The present study sought to examine the interrelationship between nitric oxide (NO) and vasoactive intestinal peptide (VIP) in myocardial protection. Isolated rat hearts were perfused for 15 min with buffer only (Group I); 0.3 mM VIP (Group II); 3 mM L-arginine (a precursor of NO) (Group III); VIP and aminoguanidine (iNOS blocker) (Group IV); or L-arginine plus VIP 10-28 (VIP inhibitor) (Group V). Each heart was then made globally ischemic for 30 min followed by 2 h reperfusion. Both VIP and NO were found to provide cardioprotection during ischemia and reperfusion. However, the beneficial effects of VIP and NO were reduced by inhibition of NO and VIP, respectively, suggesting that cardioprotection by VIP is modulated by NO and vice versa. The results of this study suggested a coordinated regulation by cardioprotection by NO and VIP.

Topics: Animals; Arginine; Cardiotonic Agents; Enzyme Inhibitors; Guanidines; Heart; In Vitro Techniques; Models, Cardiovascular; Myocardial Ischemia; Myocardial Reperfusion; Myocardial Reperfusion Injury; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Peptide Fragments; Rats; Signal Transduction; Stereoisomerism; Vasoactive Intestinal Peptide; Vasodilation