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NO‐ and non‐NO‐, Non‐Prostanoid‐Dependent Vasodilatation in Rat Sciatic Nerve During Maturation and Developing Experimental Diabetic Neuropathy
Author(s) -
Thomsen Kirsten,
Rubin Inger,
Lauritzen Martin
Publication year - 2002
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2002.023564
Subject(s) - vasodilation , medicine , endocrinology , pinacidil , diabetes mellitus , prostanoid , acetylcholine , streptozotocin , vasoconstriction , glibenclamide , prostaglandin
This study examined NO‐ and non‐NO‐, non‐prostanoid‐dependent pathways of agonist‐induced vasodilatation in streptozotocin (STZ)‐induced diabetic rats and their age‐matched controls at 1–2, 8–10 and 18–20 weeks after induction of diabetes. Using laser Doppler flowmetry, vasodilatory responses to acetylcholine (ACh; 0.1 mM) and morpholino‐sydnonimine (SIN‐1) were determined in the presence of Ringer solution, during inhibition of NO synthase (NOS) and cyclo‐oxygenase (COX) with N ω ‐nitro‐L‐arginine (L‐NNA; 1 mM) + indomethacin (10 −5 M), and during inhibition of K + channels, NOS and COX with tetraethylammonium (TEA; 10 mM) + L‐NNA + indomethacin. Basal NOS activity and nerve conduction velocity were also determined. In age‐matched controls, SIN‐1‐induced vasodilatation in the presence of TEA + L‐NNA + indomethacin, basal NOS activity and the initial vasodilatory response to ACh during NOS and COX inhibition all decreased with maturation. In STZ‐induced diabetics, SIN‐1‐induced vasodilatation in the presence of TEA + L‐NNA + indomethacin was impaired immediately after induction of diabetes, but not at 18–20 weeks. NOS activity in STZ‐induced diabetics displayed a transient 2‐fold increase at 8–10 weeks, decreasing to age‐matched control levels at 18–20 weeks. At 18–20 weeks of STZ‐induced diabetes, ACh‐induced vasodilatation during NOS and COX inhibition was prolonged due to increased K + channel activity and experimental diabetic sensory neuropathy (EDN) had developed. Thus, in sciatic nerve microcirculation of STZ‐induced diabetic rats: (1) diabetic impairment of vasodilatation in response to exogenous NO was transient; (2) non‐NO‐, non‐prostanoid‐dependent vasodilatation and K + channel activity were augmented in STZ‐induced diabetes; and (3) alterations in NO bioactivity were not related to the development of EDN.