Aminoguanidine effects on nerve blood flow, vascular permeability, electrophysiology, and oxygen free radicals

M. Kihara, J. D. Schmelzer, J. F. Poduslo, G. L. Curran, K. K. Nickander, Phillip Anson Low

Research output: Contribution to journalArticle

192 Citations (Scopus)

Abstract

Since advanced glycosylation end products have been suggested to mediate hyperglycemia-induced microvascular atherogenesis and because aminoguanidine (AG) prevents their generation, we examined whether AG could prevent or ameliorate the physiologic and biochemical indices of streptozotocin (STZ)-induced experimental diabetic neuropathy. Four groups of adult Sprague-Dawley rats were studied: group I received STZ plus AG (25 mg·kg-1·day-1), group II received STZ plus AG (50 mg·kg-1·day-1), group III received STZ alone, and group IV was a control. We monitored conduction and action potential amplitudes serially in sciatic-tibial and caudal nerves, nerve blood flow, oxygen free radical activity (conjugated dienes and hydroperoxides), and the product of the permeability coefficient and surface area to 125I-labeled albumin. STZ-induced diabetes (group III) caused a 57% reduction in nerve blood flow and in abnormal nerve conduction and amplitudes and a 60% increase in conjugated dienes. Nerve blood flow was normalized by 8 weeks with AG (groups I and II) and conduction was significantly improved, in a dose-dependent manner, by 16 and 24 weeks in sciatic-tibial and caudal nerves, respectively. The permeability coefficient was not impaired, suggesting a normal blood-nerve barrier function for albumin, and the oxygen free-radical indices were not ameliorated by AG. We suggest that AG reverses nerve ischemia and more gradually improves their electrophysiology by an action on nerve microvessels. AG may have potential in the treatment of diabetic neuropathy.

Original languageEnglish (US)
Pages (from-to)6107-6111
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number14
StatePublished - 1991

Fingerprint

Electrophysiology
Capillary Permeability
Free Radicals
Reactive Oxygen Species
Streptozocin
Tibial Nerve
Diabetic Neuropathies
Albumins
Permeability
Blood-Nerve Barrier
Advanced Glycosylation End Products
Experimental Diabetes Mellitus
pimagedine
Neural Conduction
Microvessels
Hyperglycemia
Hydrogen Peroxide
Action Potentials
Sprague Dawley Rats
Atherosclerosis

Keywords

  • diabetic neuropathy
  • hyperglycemia
  • microvascular atherogenesis
  • streptozotocin

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Aminoguanidine effects on nerve blood flow, vascular permeability, electrophysiology, and oxygen free radicals. / Kihara, M.; Schmelzer, J. D.; Poduslo, J. F.; Curran, G. L.; Nickander, K. K.; Low, Phillip Anson.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 88, No. 14, 1991, p. 6107-6111.

Research output: Contribution to journalArticle

@article{12339fff1e5f4e9090002adddc88fc47,
title = "Aminoguanidine effects on nerve blood flow, vascular permeability, electrophysiology, and oxygen free radicals",
abstract = "Since advanced glycosylation end products have been suggested to mediate hyperglycemia-induced microvascular atherogenesis and because aminoguanidine (AG) prevents their generation, we examined whether AG could prevent or ameliorate the physiologic and biochemical indices of streptozotocin (STZ)-induced experimental diabetic neuropathy. Four groups of adult Sprague-Dawley rats were studied: group I received STZ plus AG (25 mg·kg-1·day-1), group II received STZ plus AG (50 mg·kg-1·day-1), group III received STZ alone, and group IV was a control. We monitored conduction and action potential amplitudes serially in sciatic-tibial and caudal nerves, nerve blood flow, oxygen free radical activity (conjugated dienes and hydroperoxides), and the product of the permeability coefficient and surface area to 125I-labeled albumin. STZ-induced diabetes (group III) caused a 57{\%} reduction in nerve blood flow and in abnormal nerve conduction and amplitudes and a 60{\%} increase in conjugated dienes. Nerve blood flow was normalized by 8 weeks with AG (groups I and II) and conduction was significantly improved, in a dose-dependent manner, by 16 and 24 weeks in sciatic-tibial and caudal nerves, respectively. The permeability coefficient was not impaired, suggesting a normal blood-nerve barrier function for albumin, and the oxygen free-radical indices were not ameliorated by AG. We suggest that AG reverses nerve ischemia and more gradually improves their electrophysiology by an action on nerve microvessels. AG may have potential in the treatment of diabetic neuropathy.",
keywords = "diabetic neuropathy, hyperglycemia, microvascular atherogenesis, streptozotocin",
author = "M. Kihara and Schmelzer, {J. D.} and Poduslo, {J. F.} and Curran, {G. L.} and Nickander, {K. K.} and Low, {Phillip Anson}",
year = "1991",
language = "English (US)",
volume = "88",
pages = "6107--6111",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "14",

}

TY - JOUR

T1 - Aminoguanidine effects on nerve blood flow, vascular permeability, electrophysiology, and oxygen free radicals

AU - Kihara, M.

AU - Schmelzer, J. D.

AU - Poduslo, J. F.

AU - Curran, G. L.

AU - Nickander, K. K.

AU - Low, Phillip Anson

PY - 1991

Y1 - 1991

N2 - Since advanced glycosylation end products have been suggested to mediate hyperglycemia-induced microvascular atherogenesis and because aminoguanidine (AG) prevents their generation, we examined whether AG could prevent or ameliorate the physiologic and biochemical indices of streptozotocin (STZ)-induced experimental diabetic neuropathy. Four groups of adult Sprague-Dawley rats were studied: group I received STZ plus AG (25 mg·kg-1·day-1), group II received STZ plus AG (50 mg·kg-1·day-1), group III received STZ alone, and group IV was a control. We monitored conduction and action potential amplitudes serially in sciatic-tibial and caudal nerves, nerve blood flow, oxygen free radical activity (conjugated dienes and hydroperoxides), and the product of the permeability coefficient and surface area to 125I-labeled albumin. STZ-induced diabetes (group III) caused a 57% reduction in nerve blood flow and in abnormal nerve conduction and amplitudes and a 60% increase in conjugated dienes. Nerve blood flow was normalized by 8 weeks with AG (groups I and II) and conduction was significantly improved, in a dose-dependent manner, by 16 and 24 weeks in sciatic-tibial and caudal nerves, respectively. The permeability coefficient was not impaired, suggesting a normal blood-nerve barrier function for albumin, and the oxygen free-radical indices were not ameliorated by AG. We suggest that AG reverses nerve ischemia and more gradually improves their electrophysiology by an action on nerve microvessels. AG may have potential in the treatment of diabetic neuropathy.

AB - Since advanced glycosylation end products have been suggested to mediate hyperglycemia-induced microvascular atherogenesis and because aminoguanidine (AG) prevents their generation, we examined whether AG could prevent or ameliorate the physiologic and biochemical indices of streptozotocin (STZ)-induced experimental diabetic neuropathy. Four groups of adult Sprague-Dawley rats were studied: group I received STZ plus AG (25 mg·kg-1·day-1), group II received STZ plus AG (50 mg·kg-1·day-1), group III received STZ alone, and group IV was a control. We monitored conduction and action potential amplitudes serially in sciatic-tibial and caudal nerves, nerve blood flow, oxygen free radical activity (conjugated dienes and hydroperoxides), and the product of the permeability coefficient and surface area to 125I-labeled albumin. STZ-induced diabetes (group III) caused a 57% reduction in nerve blood flow and in abnormal nerve conduction and amplitudes and a 60% increase in conjugated dienes. Nerve blood flow was normalized by 8 weeks with AG (groups I and II) and conduction was significantly improved, in a dose-dependent manner, by 16 and 24 weeks in sciatic-tibial and caudal nerves, respectively. The permeability coefficient was not impaired, suggesting a normal blood-nerve barrier function for albumin, and the oxygen free-radical indices were not ameliorated by AG. We suggest that AG reverses nerve ischemia and more gradually improves their electrophysiology by an action on nerve microvessels. AG may have potential in the treatment of diabetic neuropathy.

KW - diabetic neuropathy

KW - hyperglycemia

KW - microvascular atherogenesis

KW - streptozotocin

UR - http://www.scopus.com/inward/record.url?scp=0025787122&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025787122&partnerID=8YFLogxK

M3 - Article

C2 - 2068089

AN - SCOPUS:0025787122

VL - 88

SP - 6107

EP - 6111

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 14

ER -