Blockade of nitric oxide decreases the renal vasodilatory effect of neuropeptide Y in the insulin-treated diabetic rat.
The effect of 50 days of streptozotocine-induced diabetes mellitus (blood glucose 20 mmol/l) on contraction and relaxation of isolated renal and intrarenal arteries in rats were examined. Strong and similar contractions were induced by potassium (60 mM), 5-hydroxytryptamine (5-HT) and endothelin-1 (ET-1) in renal and intrarenal arteries in diabetic and control rats. The vasodilatory reactivity, after precontraction with 5-HT, of neuropeptide Y (NPY) was similar to that of acetylcholine (ACh), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) and was similar in diabetic and control rats. The relaxing effect of NPY was decreased (40%) only in the diabetic group by blockade of nitric oxide synthase with NG-nitro-L-arginine methyl ester (10(-4) M) and by blockade (50%) of NPY with alpha-trinositol (10(-6) M). In conclusion, the present study showed that diabetes mellitus in the rat is associated with normal vasoconstrictive and vasodilatory capacities. However, the vasodilatory response to NPY was largely eliminated by blockade of nitric oxide synthesis only in the diabetic animals. This indicates that the vasodilatory effect of NPY in diabetes mellitus may be dependent on nitric oxide synthesis.
Torffvit
O
O
Department of Internal Medicine, University Hospital, S-221 85 Lund, Sweden.
Edvinsson
L
L
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects*; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
D007328:Insulin; D009478:Neuropeptide Y; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009569:Nitric Oxide