TY - JOUR

T1 - NO- and non-NO-, non-prostanoid-dependent vasodilatation in rat sciatic nerve during maturation and developing experimental diabetic neuropathy

AU - Thomsen, Kirsten

AU - Rubin, Inger

AU - Lauritzen, Martin

PY - 2002/9/15

Y1 - 2002/9/15

N2 - 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 Nω-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.

AB - 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 Nω-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.

UR - http://www.scopus.com/inward/record.url?scp=0037106520&partnerID=8YFLogxK

U2 - 10.1113/jphysiol.2002.023564

DO - 10.1113/jphysiol.2002.023564

M3 - Journal article

C2 - 12231652

AN - SCOPUS:0037106520

VL - 543

SP - 977

EP - 993

JO - The Journal of Physiology

JF - The Journal of Physiology

SN - 0022-3751

IS - 3

ER -