L-arginine does not reverse impaired agonist-induced increases in macromolecular efflux during diabetes mellitus

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Abstract

Objective: The first goal of this study was to determine the effect of diabetes mellitus on agonist induced increases in venular macromolecular permeability of the hamster cheek pouch. The second goal was examine the role for an alteration in the availability of L-arginine to nitric oxide synthase in impaired agonist-induced increases in macromolecular permeability during diabetes. Methods: We used intravital fluorescent microscopy and fluorescein isothiocyanate dextran (FITC-dextran; mw = 70 K) to examine macromolecular extravasation from post-capillary venules in non-diabetic and diabetic (2 weeks after injection of streptozotocin) hamsters in response to histamine and substance P. Increases in extravasation of macromolecules were quantitated by counting the number of venular leaky sites and by calculating the clearance (ml/s x 10-6) of FITC-dextran-70K. Results: In non-diabetic hamsters, histamine (1.0 and 5.0 μM) and substance P (50 and 100 nM) increased permeability of the cheek pouch microcirculation to FITC-dextran- 70K. In contrast, histamine- and substance P-induced increases in macromolecular extravasation were markedly reduced in diabetic hamsters. Next, we investigated whether alterations in histamine- and substance P- induced changes in macromolecular extravasation in diabetic hamsters may be related to an alteration in the availability of L-arginine. We examined whether exogenous application of L-arginine (100 μM) could restore impaired histamine- and substance-P-induced increases in macromolecular extravasation in diabetic hamsters. We found that L-arginine potentiated agonist-induced increases in macromolecular extravasation in non-diabetic hamsters, but did not alter responses in diabetic hamsters. Conclusion: These findings suggest that short-term diabetes mellitus alters agonist-induced alterations in microvascular permeability. The mechanism of altered microvascular permeability during diabetes mellitus does not appear to be related to an impaired availability of L-arginine.

Original languageEnglish (US)
Pages (from-to)215-222
Number of pages8
JournalCardiovascular research
Volume34
Issue number1
DOIs
StatePublished - Apr 1 1997

Fingerprint

Cricetinae
Arginine
Diabetes Mellitus
Substance P
Histamine
Permeability
Cheek
Capillary Permeability
Venules
Microcirculation
Streptozocin
Dextrans
Nitric Oxide Synthase
Injections
fluorescein isothiocyanate dextran

Keywords

  • Cheek pouch
  • Diabetes
  • Hamster
  • Histamine
  • Immunofluorescence
  • L-Arginine
  • Nitric oxide
  • Permeability
  • Substance- P

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

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title = "L-arginine does not reverse impaired agonist-induced increases in macromolecular efflux during diabetes mellitus",
abstract = "Objective: The first goal of this study was to determine the effect of diabetes mellitus on agonist induced increases in venular macromolecular permeability of the hamster cheek pouch. The second goal was examine the role for an alteration in the availability of L-arginine to nitric oxide synthase in impaired agonist-induced increases in macromolecular permeability during diabetes. Methods: We used intravital fluorescent microscopy and fluorescein isothiocyanate dextran (FITC-dextran; mw = 70 K) to examine macromolecular extravasation from post-capillary venules in non-diabetic and diabetic (2 weeks after injection of streptozotocin) hamsters in response to histamine and substance P. Increases in extravasation of macromolecules were quantitated by counting the number of venular leaky sites and by calculating the clearance (ml/s x 10-6) of FITC-dextran-70K. Results: In non-diabetic hamsters, histamine (1.0 and 5.0 μM) and substance P (50 and 100 nM) increased permeability of the cheek pouch microcirculation to FITC-dextran- 70K. In contrast, histamine- and substance P-induced increases in macromolecular extravasation were markedly reduced in diabetic hamsters. Next, we investigated whether alterations in histamine- and substance P- induced changes in macromolecular extravasation in diabetic hamsters may be related to an alteration in the availability of L-arginine. We examined whether exogenous application of L-arginine (100 μM) could restore impaired histamine- and substance-P-induced increases in macromolecular extravasation in diabetic hamsters. We found that L-arginine potentiated agonist-induced increases in macromolecular extravasation in non-diabetic hamsters, but did not alter responses in diabetic hamsters. Conclusion: These findings suggest that short-term diabetes mellitus alters agonist-induced alterations in microvascular permeability. The mechanism of altered microvascular permeability during diabetes mellitus does not appear to be related to an impaired availability of L-arginine.",
keywords = "Cheek pouch, Diabetes, Hamster, Histamine, Immunofluorescence, L-Arginine, Nitric oxide, Permeability, Substance- P",
author = "Mayhan, {William G.}",
year = "1997",
month = "4",
day = "1",
doi = "10.1016/S0008-6363(97)00013-8",
language = "English (US)",
volume = "34",
pages = "215--222",
journal = "Cardiovascular Research",
issn = "0008-6363",
publisher = "Oxford University Press",
number = "1",

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TY - JOUR

T1 - L-arginine does not reverse impaired agonist-induced increases in macromolecular efflux during diabetes mellitus

AU - Mayhan, William G.

PY - 1997/4/1

Y1 - 1997/4/1

N2 - Objective: The first goal of this study was to determine the effect of diabetes mellitus on agonist induced increases in venular macromolecular permeability of the hamster cheek pouch. The second goal was examine the role for an alteration in the availability of L-arginine to nitric oxide synthase in impaired agonist-induced increases in macromolecular permeability during diabetes. Methods: We used intravital fluorescent microscopy and fluorescein isothiocyanate dextran (FITC-dextran; mw = 70 K) to examine macromolecular extravasation from post-capillary venules in non-diabetic and diabetic (2 weeks after injection of streptozotocin) hamsters in response to histamine and substance P. Increases in extravasation of macromolecules were quantitated by counting the number of venular leaky sites and by calculating the clearance (ml/s x 10-6) of FITC-dextran-70K. Results: In non-diabetic hamsters, histamine (1.0 and 5.0 μM) and substance P (50 and 100 nM) increased permeability of the cheek pouch microcirculation to FITC-dextran- 70K. In contrast, histamine- and substance P-induced increases in macromolecular extravasation were markedly reduced in diabetic hamsters. Next, we investigated whether alterations in histamine- and substance P- induced changes in macromolecular extravasation in diabetic hamsters may be related to an alteration in the availability of L-arginine. We examined whether exogenous application of L-arginine (100 μM) could restore impaired histamine- and substance-P-induced increases in macromolecular extravasation in diabetic hamsters. We found that L-arginine potentiated agonist-induced increases in macromolecular extravasation in non-diabetic hamsters, but did not alter responses in diabetic hamsters. Conclusion: These findings suggest that short-term diabetes mellitus alters agonist-induced alterations in microvascular permeability. The mechanism of altered microvascular permeability during diabetes mellitus does not appear to be related to an impaired availability of L-arginine.

AB - Objective: The first goal of this study was to determine the effect of diabetes mellitus on agonist induced increases in venular macromolecular permeability of the hamster cheek pouch. The second goal was examine the role for an alteration in the availability of L-arginine to nitric oxide synthase in impaired agonist-induced increases in macromolecular permeability during diabetes. Methods: We used intravital fluorescent microscopy and fluorescein isothiocyanate dextran (FITC-dextran; mw = 70 K) to examine macromolecular extravasation from post-capillary venules in non-diabetic and diabetic (2 weeks after injection of streptozotocin) hamsters in response to histamine and substance P. Increases in extravasation of macromolecules were quantitated by counting the number of venular leaky sites and by calculating the clearance (ml/s x 10-6) of FITC-dextran-70K. Results: In non-diabetic hamsters, histamine (1.0 and 5.0 μM) and substance P (50 and 100 nM) increased permeability of the cheek pouch microcirculation to FITC-dextran- 70K. In contrast, histamine- and substance P-induced increases in macromolecular extravasation were markedly reduced in diabetic hamsters. Next, we investigated whether alterations in histamine- and substance P- induced changes in macromolecular extravasation in diabetic hamsters may be related to an alteration in the availability of L-arginine. We examined whether exogenous application of L-arginine (100 μM) could restore impaired histamine- and substance-P-induced increases in macromolecular extravasation in diabetic hamsters. We found that L-arginine potentiated agonist-induced increases in macromolecular extravasation in non-diabetic hamsters, but did not alter responses in diabetic hamsters. Conclusion: These findings suggest that short-term diabetes mellitus alters agonist-induced alterations in microvascular permeability. The mechanism of altered microvascular permeability during diabetes mellitus does not appear to be related to an impaired availability of L-arginine.

KW - Cheek pouch

KW - Diabetes

KW - Hamster

KW - Histamine

KW - Immunofluorescence

KW - L-Arginine

KW - Nitric oxide

KW - Permeability

KW - Substance- P

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