Acetylcholine-induced arteriolar dilation is reduced in streptozotocin-induced diabetic rats with motor nerve dysfunction

K Terata; L J Coppey; E P Davidson; J A Dunlap; D D Gutterman; M A Yorek

doi:10.1038/sj.bjp.0702856

Back

Acetylcholine-induced arteriolar dilation is reduced in streptozotocin-induced diabetic rats with motor nerve dysfunction

Journal article

Open access

Peer reviewed

Acetylcholine-induced arteriolar dilation is reduced in streptozotocin-induced diabetic rats with motor nerve dysfunction

K Terata, L J Coppey, E P Davidson, J A Dunlap, D D Gutterman and M A Yorek

British journal of pharmacology, Vol.128(3), pp.837-843

10/1999

DOI: 10.1038/sj.bjp.0702856

PMCID: PMC1571695

PMID: 10516670

Files and links (1)

url

https://doi.org/10.1038/sj.bjp.0702856View

Published (Version of record) Open Access

Abstract

1. Diabetes mellitus produces marked abnormalities in motor nerve conduction, but the mechanism is not clear. In the present study we hypothesized that in the streptozotocin (STZ)-induced diabetic rat impaired vasodilator function is associated with reduced endoneural blood flow (EBF) which may contribute to nerve dysfunction. 2. We examined whether diabetes-induced reductions in sciatic nerve conduction velocity and EBF were associated with impaired endothelium-dependent dilation in adjacent arterioles. We measured motor nerve conduction velocity (MNCV) in the sciatic nerve using a non-invasive procedure, and sciatic nerve nutritive blood flow using microelectrode polarography and hydrogen clearance. In vitro videomicroscopy was used to quantify arteriolar diameter responses to dilator agonists in arterioles overlying the sciatic nerve. 3. MNCV and EBF in 4-week-STZ-induced diabetic rats were decreased by 22% and 49% respectively. Arterioles were constricted with U46619 and dilation to acetylcholine (ACh), aprikalim, or sodium nitroprusside (SNP) examined. All agonists elicited dose-dependent dilation in control and diabetic rats, although ACh-induced dilation was significantly reduced in diabetic rats. Treating vessels from normal or diabetic rats with indomethacin (INDO) alone did not significantly affect ACh-induced relaxation. However, ACh-induced vasodilation was significantly reduced by treatment with KCl or Nomega-nitro-L-arginine (LNNA) alone. Combining LNNA and KCl further reduced ACh-induced dilation in these vessels. 4. Diabetes causes vasodilator dysfunction in a microvascular bed that provides circulation to the sciatic nerve. These studies imply that ACh-induced dilation in these vessels is mediated by multiple mechanisms that may include the endothelial-dependent production of nitric oxide and endothelial-derived hyperpolarizing factor. This impaired vascular response is associated with neural dysfunction.

Arterioles - physiology

Motor Neurons - physiology

Body Weight

Vasodilator Agents - pharmacology

Acetylcholine - pharmacology

Streptozocin

Rats

Male

Sciatic Nerve - blood supply

Arterioles - drug effects

Rats, Sprague-Dawley

Regional Blood Flow

Diabetes Mellitus, Experimental - blood

Animals

Blood Glucose - metabolism

Diabetes Mellitus, Experimental - physiopathology

Details

Title: Subtitle: Acetylcholine-induced arteriolar dilation is reduced in streptozotocin-induced diabetic rats with motor nerve dysfunction
Creators: K Terata - Veterans Affairs Medical Center, Diabetes Endocrinology Research Center and Department of Internal Medicine, University of Iowa, Iowa City, IA 52246, USA
L J Coppey
E P Davidson
J A Dunlap
D D Gutterman
M A Yorek
Resource Type: Journal article
Publication Details: British journal of pharmacology, Vol.128(3), pp.837-843
DOI: 10.1038/sj.bjp.0702856
PMID: 10516670
PMCID: PMC1571695
ISSN: 0007-1188
eISSN: 1476-5381
Grant note: DK-25295 / NIDDK NIH HHS
Language: English
Date published: 10/1999
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984094666602771

Metrics

18 Record Views

49 Times Cited - Web of Science