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 language||English (US)|
|Journal||American Journal of Physiology - Heart and Circulatory Physiology|
|Issue number||2 49-2|
|State||Published - Feb 2001|
- Protein kinase C
ASJC Scopus subject areas
- Physiology (medical)