Decreased contractile response to endothelin-1 of peripheral microvasculature from diabetic patients

Jun Feng, Yuhong Liu, Kamal R. Khabbaz, Robert Hagberg, Michael P. Robich, Richard T. Clements, Cesario Bianchi, Frank W. Sellke

Research output: Contribution to journalArticlepeer-review

Abstract

Background: We compared the contractile responses to endothelin-1 (ET-1) with and without the inhibition of ET-A receptors and protein kinase C-alpha (PKC-α) in the human peripheral microvasculature of diabetic and case-matched, nondiabetic patients. Methods: Chest wall skeletal muscle was harvested from patients with and without diabetics undergoing cardiac surgery. Peripheral arterioles (90-180 μm in diameter) were dissected from the harvested tissue. Microvascular constriction was assessed by videomicroscopy in response to ET-1 with and without an endothelin-A (ET-A) receptor antagonist, an endothelin B (ET-B) antagonist, or a PKC-α inhibitor. Results: ET-1 induced a dose-dependent contractile response of skeletal muscle arterioles from diabetic and nondiabetic patients. The contractile response of diabetic arterioles from both prebypass and postbypass to ET-1 (10-9 mol/L) was decreased compared with those of nondiabetic patients (P < .05). The contractile responses of microvessels of both diabetics and nondiabetics to ET-1 were inhibited in the presence of either ET-A receptor antagonist BQ123 (10-7 mol/L) or the PKC-α inhibitor safingol (2 × 10 -5 mol/L, P < .05, respectively). In contrast, the ET-1-induced vasoconstriction was not affected by the administration of the ET-B receptor antagonist BQ788 (10-7 mol/L). There were no differences in skeletal muscle levels of the ET-A and ET-B receptors between diabetic and nondiabetic groups. Conclusion: Diabetic patients demonstrated a decreased contractile response to ET-1 in human peripheral microvasculature. The contractile response of diabetic vessels to ET-1 occurs via activation of ET-A receptors and PKC-α. These results provide novel mechanisms of ET-1-induced contraction in vasomotor dysfunction in patients with diabetes.

Original languageEnglish (US)
Pages (from-to)247-252
Number of pages6
JournalSurgery
Volume149
Issue number2
DOIs
StatePublished - Feb 2011
Externally publishedYes

ASJC Scopus subject areas

  • Surgery

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