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Evaluation of activation of protein kinase C during agonist-induced constriction of veins isolated from the laminar dermis of horses

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  • 1 Department of Physiology and Pharmacology, Institute of Comparative Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389
  • | 2 Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389
  • | 3 Department of Physiology and Pharmacology, Institute of Comparative Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389
  • | 4 Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389
  • | 5 Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389
  • | 6 Department of Physiology and Pharmacology, Institute of Comparative Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389
  • | 7 Department of Physiology and Pharmacology, Institute of Comparative Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389
  • | 8 Department of Physiology and Pharmacology, Institute of Comparative Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389
  • | 9 Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389

Abstract

Objective—To determine the effects of the protein kinase C (PKC) inhibitor, Ro-31-8220, on agonist-induced constriction of laminar arteries and veins obtained from horses.

Sample Population—Laminar arteries and veins obtained from 8 adult mixed-breed horses.

Procedures—Laminar arteries and veins were isolated and mounted on small vessel myographs for the measurement of isometric tension. Concentration-response curves were then obtained for the vasoconstrictor agonists phenylephrine, 5-hydroxytryptamine, prostaglandin F, and endothelin-1. All responses were measured with or without the addition of Ro-31-8220 (3μM).

Results—Laminar veins were more sensitive to vasoconstrictor agonists than laminar arteries, and incubation of laminar veins with Ro-31-8220 resulted in significantly smaller agonist-induced contractile responses for all agonists tested. In contrast, Ro-31-8220 had no effect on agonist-induced contractile responses of laminar arteries.

Conclusions and Clinical Relevance—Results of the study were consistent with activation of PKC being confined to agonist-induced contraction of laminar veins isolated from the laminar dermis of horses. Consequently, the possible involvement of PKC in the venoconstriction observed during the development of laminitis is worthy of further investigation.

Abstract

Objective—To determine the effects of the protein kinase C (PKC) inhibitor, Ro-31-8220, on agonist-induced constriction of laminar arteries and veins obtained from horses.

Sample Population—Laminar arteries and veins obtained from 8 adult mixed-breed horses.

Procedures—Laminar arteries and veins were isolated and mounted on small vessel myographs for the measurement of isometric tension. Concentration-response curves were then obtained for the vasoconstrictor agonists phenylephrine, 5-hydroxytryptamine, prostaglandin F, and endothelin-1. All responses were measured with or without the addition of Ro-31-8220 (3μM).

Results—Laminar veins were more sensitive to vasoconstrictor agonists than laminar arteries, and incubation of laminar veins with Ro-31-8220 resulted in significantly smaller agonist-induced contractile responses for all agonists tested. In contrast, Ro-31-8220 had no effect on agonist-induced contractile responses of laminar arteries.

Conclusions and Clinical Relevance—Results of the study were consistent with activation of PKC being confined to agonist-induced contraction of laminar veins isolated from the laminar dermis of horses. Consequently, the possible involvement of PKC in the venoconstriction observed during the development of laminitis is worthy of further investigation.

Contributor Notes

Supported by the National Research Initiative of the USDA Cooperative State Research, Education and Extension Service (grants No. 2003-35204-13350 and 2002-35204-12423); the Morris Animal Foundation; the White Fox Farm Research Fund; and Pfizer Animal Health.

The authors thank Megan E. Grafton and Maria Aceves-Avila for technical assistance.

Address correspondence to Dr. Robertson.