Discordant effects of guanidines on renal structure and function and on regional vascular dysfunction and collagen changes in diabetic rats

Jens R. Nyengaard, Katherine Chang, Susan Berhorst, Karen M. Reiser, Joseph R. Williamson, Ronald Tilton

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

We examined the effects of aminoguanidine and methylguanidine on vascular dysfunction, glomerular structural changes, and indexes of early and late nonenzymatic glycation in 7-month streptozotocin-induced diabetic rats. Kidney weight, glomerular volume, fractional mesangial volume, glomerular capillary basement membrane width, and urinary albumin excretion were increased in diabetic rats. Diabetes also 1) increased vascular albumin permeation twofold in retina, sciatic nerve, aorta, skin, and kidney; 2) decreased renal collagenase-soluble collagen; 3) increased collagen- associated fluorescence in kidney and skin but not in aorta; and 4) increased glycated hemoglobin levels and aortic pentosidine levels. Aminoguanidine reduced albuminuria by 70% after 4 months, and both guanidines 1) normalized aortic pentosidine levels and renal collagenase-soluble collagen, 2) had no effect on glycated hemoglobin levels or collagen-associated fluorescence (in aorta, kidney, or skin), and 3) had little or no effect on regional albumin permeation. These discordant effects of aminoguanidine on diabetes-induced vascular changes versus parameters of nonenzymatic glycation are consistent with a multifactorial pathogenesis of diabetic complications, including roles for metabolic imbalances independent of nonenzymatic glycation. To the extent that glomerular matrix accumulation and increased regional albumin permeation in chronically diabetic rats are sequelae of nonenzymatic glycation, these findings point to an important role for early glycation reactions and products.

Original languageEnglish (US)
Pages (from-to)94-106
Number of pages13
JournalDiabetes
Volume46
Issue number1
StatePublished - Jan 1997
Externally publishedYes

Fingerprint

Guanidines
Blood Vessels
Collagen
Kidney
Albumins
Aorta
Glycosylated Hemoglobin A
Collagenases
Skin
Methylguanidine
Fluorescence
Glomerular Basement Membrane
Albuminuria
Sciatic Nerve
Diabetes Complications
Streptozocin
Retina
Weights and Measures

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Nyengaard, J. R., Chang, K., Berhorst, S., Reiser, K. M., Williamson, J. R., & Tilton, R. (1997). Discordant effects of guanidines on renal structure and function and on regional vascular dysfunction and collagen changes in diabetic rats. Diabetes, 46(1), 94-106.

Discordant effects of guanidines on renal structure and function and on regional vascular dysfunction and collagen changes in diabetic rats. / Nyengaard, Jens R.; Chang, Katherine; Berhorst, Susan; Reiser, Karen M.; Williamson, Joseph R.; Tilton, Ronald.

In: Diabetes, Vol. 46, No. 1, 01.1997, p. 94-106.

Research output: Contribution to journalArticle

Nyengaard, JR, Chang, K, Berhorst, S, Reiser, KM, Williamson, JR & Tilton, R 1997, 'Discordant effects of guanidines on renal structure and function and on regional vascular dysfunction and collagen changes in diabetic rats', Diabetes, vol. 46, no. 1, pp. 94-106.
Nyengaard, Jens R. ; Chang, Katherine ; Berhorst, Susan ; Reiser, Karen M. ; Williamson, Joseph R. ; Tilton, Ronald. / Discordant effects of guanidines on renal structure and function and on regional vascular dysfunction and collagen changes in diabetic rats. In: Diabetes. 1997 ; Vol. 46, No. 1. pp. 94-106.
@article{dd092bc9dd154f29a522372a576f5b85,
title = "Discordant effects of guanidines on renal structure and function and on regional vascular dysfunction and collagen changes in diabetic rats",
abstract = "We examined the effects of aminoguanidine and methylguanidine on vascular dysfunction, glomerular structural changes, and indexes of early and late nonenzymatic glycation in 7-month streptozotocin-induced diabetic rats. Kidney weight, glomerular volume, fractional mesangial volume, glomerular capillary basement membrane width, and urinary albumin excretion were increased in diabetic rats. Diabetes also 1) increased vascular albumin permeation twofold in retina, sciatic nerve, aorta, skin, and kidney; 2) decreased renal collagenase-soluble collagen; 3) increased collagen- associated fluorescence in kidney and skin but not in aorta; and 4) increased glycated hemoglobin levels and aortic pentosidine levels. Aminoguanidine reduced albuminuria by 70{\%} after 4 months, and both guanidines 1) normalized aortic pentosidine levels and renal collagenase-soluble collagen, 2) had no effect on glycated hemoglobin levels or collagen-associated fluorescence (in aorta, kidney, or skin), and 3) had little or no effect on regional albumin permeation. These discordant effects of aminoguanidine on diabetes-induced vascular changes versus parameters of nonenzymatic glycation are consistent with a multifactorial pathogenesis of diabetic complications, including roles for metabolic imbalances independent of nonenzymatic glycation. To the extent that glomerular matrix accumulation and increased regional albumin permeation in chronically diabetic rats are sequelae of nonenzymatic glycation, these findings point to an important role for early glycation reactions and products.",
author = "Nyengaard, {Jens R.} and Katherine Chang and Susan Berhorst and Reiser, {Karen M.} and Williamson, {Joseph R.} and Ronald Tilton",
year = "1997",
month = "1",
language = "English (US)",
volume = "46",
pages = "94--106",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "1",

}

TY - JOUR

T1 - Discordant effects of guanidines on renal structure and function and on regional vascular dysfunction and collagen changes in diabetic rats

AU - Nyengaard, Jens R.

AU - Chang, Katherine

AU - Berhorst, Susan

AU - Reiser, Karen M.

AU - Williamson, Joseph R.

AU - Tilton, Ronald

PY - 1997/1

Y1 - 1997/1

N2 - We examined the effects of aminoguanidine and methylguanidine on vascular dysfunction, glomerular structural changes, and indexes of early and late nonenzymatic glycation in 7-month streptozotocin-induced diabetic rats. Kidney weight, glomerular volume, fractional mesangial volume, glomerular capillary basement membrane width, and urinary albumin excretion were increased in diabetic rats. Diabetes also 1) increased vascular albumin permeation twofold in retina, sciatic nerve, aorta, skin, and kidney; 2) decreased renal collagenase-soluble collagen; 3) increased collagen- associated fluorescence in kidney and skin but not in aorta; and 4) increased glycated hemoglobin levels and aortic pentosidine levels. Aminoguanidine reduced albuminuria by 70% after 4 months, and both guanidines 1) normalized aortic pentosidine levels and renal collagenase-soluble collagen, 2) had no effect on glycated hemoglobin levels or collagen-associated fluorescence (in aorta, kidney, or skin), and 3) had little or no effect on regional albumin permeation. These discordant effects of aminoguanidine on diabetes-induced vascular changes versus parameters of nonenzymatic glycation are consistent with a multifactorial pathogenesis of diabetic complications, including roles for metabolic imbalances independent of nonenzymatic glycation. To the extent that glomerular matrix accumulation and increased regional albumin permeation in chronically diabetic rats are sequelae of nonenzymatic glycation, these findings point to an important role for early glycation reactions and products.

AB - We examined the effects of aminoguanidine and methylguanidine on vascular dysfunction, glomerular structural changes, and indexes of early and late nonenzymatic glycation in 7-month streptozotocin-induced diabetic rats. Kidney weight, glomerular volume, fractional mesangial volume, glomerular capillary basement membrane width, and urinary albumin excretion were increased in diabetic rats. Diabetes also 1) increased vascular albumin permeation twofold in retina, sciatic nerve, aorta, skin, and kidney; 2) decreased renal collagenase-soluble collagen; 3) increased collagen- associated fluorescence in kidney and skin but not in aorta; and 4) increased glycated hemoglobin levels and aortic pentosidine levels. Aminoguanidine reduced albuminuria by 70% after 4 months, and both guanidines 1) normalized aortic pentosidine levels and renal collagenase-soluble collagen, 2) had no effect on glycated hemoglobin levels or collagen-associated fluorescence (in aorta, kidney, or skin), and 3) had little or no effect on regional albumin permeation. These discordant effects of aminoguanidine on diabetes-induced vascular changes versus parameters of nonenzymatic glycation are consistent with a multifactorial pathogenesis of diabetic complications, including roles for metabolic imbalances independent of nonenzymatic glycation. To the extent that glomerular matrix accumulation and increased regional albumin permeation in chronically diabetic rats are sequelae of nonenzymatic glycation, these findings point to an important role for early glycation reactions and products.

UR - http://www.scopus.com/inward/record.url?scp=0031022947&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031022947&partnerID=8YFLogxK

M3 - Article

VL - 46

SP - 94

EP - 106

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 1

ER -