Arteriolar nitric oxide concentration is decreased during hyperglycemia-induced βII PKC activation

H. Bohlen, Geoffrey P. Nase

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52 Citations (Scopus)

Abstract

βII protein kinase C (βPKC) is activated during acute and chronic hyperglycemia and may alter endothelial cell function. We determined whether blockade of βPKC protected in vivo endothelial formation of NO, as measured with NO-sensitive microelectrodes in the rat intestinal vasculature. NaCl hyperosmolarity, a specific endothelial stimulus to increase NO formation, caused ∼20% arteriolar vasodilation and ∼30% increase in NO concentration ([NO]). After topical 300 mg/dl hyperglycemia for 45 min, both responses were all but abolished. In comparison, pretreatment with LY-333531, a specific βPKC inhibitor, maintained vasodilation and [NO] responses to NaCl hyperosmolarity after hyperglycemia. The βPKC inhibitor alone had no significant effects on resting diameter or [NO] or their responses to NaCl hyperosmolarity. In separate rats, after topical hyperglycemia had suppressed dilation to ACh, LY-333531 restored ∼70% of the dilatory response. These data demonstrated that activation of βPKC during acute hyperglycemia depressed in vivo endothelial formation of NO at rest and during stimulation. This abnormality can be minimized by inhibition of βPKC before hyperglycemia and can be substantially reversed by PKC inhibition after hyperglycemia-induced abnormalities have occurred.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume280
Issue number2 49-2
StatePublished - Feb 2001

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Hyperglycemia
Protein Kinase C
Nitric Oxide
ruboxistaurin
Protein C Inhibitor
Protein Kinase Inhibitors
Vasodilation
Microelectrodes
Dilatation
Endothelial Cells

Keywords

  • Arteriole
  • Protein kinase C

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

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title = "Arteriolar nitric oxide concentration is decreased during hyperglycemia-induced βII PKC activation",
abstract = "βII protein kinase C (βPKC) is activated during acute and chronic hyperglycemia and may alter endothelial cell function. We determined whether blockade of βPKC protected in vivo endothelial formation of NO, as measured with NO-sensitive microelectrodes in the rat intestinal vasculature. NaCl hyperosmolarity, a specific endothelial stimulus to increase NO formation, caused ∼20{\%} arteriolar vasodilation and ∼30{\%} increase in NO concentration ([NO]). After topical 300 mg/dl hyperglycemia for 45 min, both responses were all but abolished. In comparison, pretreatment with LY-333531, a specific βPKC inhibitor, maintained vasodilation and [NO] responses to NaCl hyperosmolarity after hyperglycemia. The βPKC inhibitor alone had no significant effects on resting diameter or [NO] or their responses to NaCl hyperosmolarity. In separate rats, after topical hyperglycemia had suppressed dilation to ACh, LY-333531 restored ∼70{\%} of the dilatory response. These data demonstrated that activation of βPKC during acute hyperglycemia depressed in vivo endothelial formation of NO at rest and during stimulation. This abnormality can be minimized by inhibition of βPKC before hyperglycemia and can be substantially reversed by PKC inhibition after hyperglycemia-induced abnormalities have occurred.",
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AU - Nase, Geoffrey P.

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N2 - βII protein kinase C (βPKC) is activated during acute and chronic hyperglycemia and may alter endothelial cell function. We determined whether blockade of βPKC protected in vivo endothelial formation of NO, as measured with NO-sensitive microelectrodes in the rat intestinal vasculature. NaCl hyperosmolarity, a specific endothelial stimulus to increase NO formation, caused ∼20% arteriolar vasodilation and ∼30% increase in NO concentration ([NO]). After topical 300 mg/dl hyperglycemia for 45 min, both responses were all but abolished. In comparison, pretreatment with LY-333531, a specific βPKC inhibitor, maintained vasodilation and [NO] responses to NaCl hyperosmolarity after hyperglycemia. The βPKC inhibitor alone had no significant effects on resting diameter or [NO] or their responses to NaCl hyperosmolarity. In separate rats, after topical hyperglycemia had suppressed dilation to ACh, LY-333531 restored ∼70% of the dilatory response. These data demonstrated that activation of βPKC during acute hyperglycemia depressed in vivo endothelial formation of NO at rest and during stimulation. This abnormality can be minimized by inhibition of βPKC before hyperglycemia and can be substantially reversed by PKC inhibition after hyperglycemia-induced abnormalities have occurred.

AB - βII protein kinase C (βPKC) is activated during acute and chronic hyperglycemia and may alter endothelial cell function. We determined whether blockade of βPKC protected in vivo endothelial formation of NO, as measured with NO-sensitive microelectrodes in the rat intestinal vasculature. NaCl hyperosmolarity, a specific endothelial stimulus to increase NO formation, caused ∼20% arteriolar vasodilation and ∼30% increase in NO concentration ([NO]). After topical 300 mg/dl hyperglycemia for 45 min, both responses were all but abolished. In comparison, pretreatment with LY-333531, a specific βPKC inhibitor, maintained vasodilation and [NO] responses to NaCl hyperosmolarity after hyperglycemia. The βPKC inhibitor alone had no significant effects on resting diameter or [NO] or their responses to NaCl hyperosmolarity. In separate rats, after topical hyperglycemia had suppressed dilation to ACh, LY-333531 restored ∼70% of the dilatory response. These data demonstrated that activation of βPKC during acute hyperglycemia depressed in vivo endothelial formation of NO at rest and during stimulation. This abnormality can be minimized by inhibition of βPKC before hyperglycemia and can be substantially reversed by PKC inhibition after hyperglycemia-induced abnormalities have occurred.

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