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Effect of voltage-gated and capacitative calcium entry blockade on agonist-induced constriction of equine laminar blood vessels

John F. PeroniDepartment of Physiology and Pharmacology, Institute of Comparative Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389
Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389

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James N. MooreDepartment of Physiology and Pharmacology, Institute of Comparative Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389
Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389

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Erik NoschkaDepartment of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389

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Tristan H. LewisDepartment of Physiology and Pharmacology, Institute of Comparative Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389

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Stephen J. LewisDepartment of Physiology and Pharmacology, Institute of Comparative Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389

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Tom P. RobertsonDepartment of Physiology and Pharmacology, Institute of Comparative Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389
Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389

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Abstract

Objective—To characterize the relative contributions of voltage-gated and capacitative Ca2+ entry to agonist-induced contractions of equine laminar arteries and veins.

Animals—16 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 obtained for the vasoconstrictor agonists phenylephrine, 5-hydroxytryptamine (5-HT), prostaglandin F (PGF), and endothelin-1 (ET-1) either in the absence of extracellular Ca2+ or in the presence of the voltage-gated Ca2+ channel inhibitor diltiazem or the putative inhibitor of capacitative Ca2+ entry, trifluoromethylphenylimidazole.

Results—In the absence of extracellular Ca2+, maximal responses of veins to 5-HT, phenylephrine, ET-1 and PGF were reduced by 80%, 50%, 50%, and 45%, respectively; responses of arteries to 5-HT, phenylephrine, and ET-1 were reduced by 95%, 90%, and 20%, respectively. Although diltiazem did not affect the maximal responses of veins to any agonist, responses of arteries to 5-HT, phenylephrine, and ET-1 were reduced by 40%, 50%, and 27%, respectively. Trifluoromethylphenylimidazole did not affect maximal responses of veins, but did reduce their contractile responses to low concentrations of ET-1 and PGF.

Conclusions and Clinical Relevance—Results suggested that the contribution of extracellular Ca2+ to laminar vessel contractile responses differs between arteries and veins and also between contractile agonists, voltage-gated Ca2+ entry is more predominant in laminar arteries than in veins, and capacitative Ca2+ entry has a minor role in agonist-induced contractile responses of laminar veins.

Abstract

Objective—To characterize the relative contributions of voltage-gated and capacitative Ca2+ entry to agonist-induced contractions of equine laminar arteries and veins.

Animals—16 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 obtained for the vasoconstrictor agonists phenylephrine, 5-hydroxytryptamine (5-HT), prostaglandin F (PGF), and endothelin-1 (ET-1) either in the absence of extracellular Ca2+ or in the presence of the voltage-gated Ca2+ channel inhibitor diltiazem or the putative inhibitor of capacitative Ca2+ entry, trifluoromethylphenylimidazole.

Results—In the absence of extracellular Ca2+, maximal responses of veins to 5-HT, phenylephrine, ET-1 and PGF were reduced by 80%, 50%, 50%, and 45%, respectively; responses of arteries to 5-HT, phenylephrine, and ET-1 were reduced by 95%, 90%, and 20%, respectively. Although diltiazem did not affect the maximal responses of veins to any agonist, responses of arteries to 5-HT, phenylephrine, and ET-1 were reduced by 40%, 50%, and 27%, respectively. Trifluoromethylphenylimidazole did not affect maximal responses of veins, but did reduce their contractile responses to low concentrations of ET-1 and PGF.

Conclusions and Clinical Relevance—Results suggested that the contribution of extracellular Ca2+ to laminar vessel contractile responses differs between arteries and veins and also between contractile agonists, voltage-gated Ca2+ entry is more predominant in laminar arteries than in veins, and capacitative Ca2+ entry has a minor role in agonist-induced contractile responses of laminar veins.

Contributor Notes

Supported by the National Research Initiative of the USDA Cooperative State Research, Education and Extension Service (grants No. 2003-35204-13350 and No. 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.