Blockade of nitric oxide decreases the renal vasodilatory effect of neuropeptide Y in the insulin-treated diabetic rat

Abstract

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.

Heterogeneity of the neuropeptide Y (NPY) contractile and relaxing receptors in horse penile small arteries

“…However, evidence has emerged recently suggesting a vasodilator role for the peptide in certain vascular beds both in vivo and in vitro models. Thus, NPY relaxes precontracted renal arteries of diabetic and nondiabetic rats (Torffvit & Edvinsson, 1997), human subcutaneous arteries and mesenteric small arteries (Gradin et al, 2003), and induces vasodilatation in cerebral arteries from different species (Kobari et al, 1993;You et al, 2001). In the present study, several results provide evidence for the existence of NPY vasodilator receptors.…”

Paradoxes of nitric oxide in the diabetic kidney

“…Corresponding to studies in other experimental settings (23,90,109), these data suggest an impairment of NO endothelial production or action in diabetic arteries, possibly mediated by the increased production of ROS and prostanoids that oppose the effects of NO. However, more recent studies in that model found unchanged responses to ACh in renal arteries from insulin-treated diabetic rats preconstricted with serotonin and even enhanced responses to insulin compared with controls (130,131). In contrast to data by Dai et al (25), enhanced re-sponses to ACh and to NOS inhibition have also been reported in renal arteries harvested from untreated alloxan-diabetic rabbits (3).…”

Neuropeptide Y effects on vasorelaxation and intestinal contraction in the Atlantic cod Gadus morhua

“…Although we suggest a vascular role for NPY in cod as in mammals, our results revealed some interesting differences between these classes of vertebrates. The vasodilatory effect is uncommon, but not unique, to cod (23,32,41,43) and demonstrates the diversified use of the same precious signal substance in different organisms. NPY is highly conserved (5,24), which implies its crucial importance whether it is inhibitory or excitatory.…”

“…Intravenous injection of dogfish, frog, and human NPY produced similar vasopressor effects in three elasmobranch species, except that human NPY lowered blood pressure in one (Portjackson shark) of the three species (33). In addition, NPY may have vasodilator effects (23,32,41,43). However, to our knowledge, there are so far no reports of a function of NPY in the teleost vasculature.…”