Effects of Rho-kinase and Src protein tyrosine kinase inhibition on agonist-induced vasoconstriction of arteries and veins of the equine laminar dermis.
OBJECTIVE
To determine the effects of inhibition of Rho-kinase or Src-family protein tyrosine kinases (srcPTK) on agonist-induced contractile responses in equine laminar arteries and veins.


METHODS
Laminar arteries and veins obtained from 13 adult mixed-breed horses.


METHODS
Laminar vessels were mounted on myographs and exposed to phenylephrine (PE), 5-hydroxytryptamine (5-HT), prostaglandin F(2) (PGF(2)), and endothelin-1 (ET-1) with or without the Rho-kinase inhibitor Y-27632 (10 microM), srcPTK inhibitor PP2 (10 microM), or a negative control analogue for PP2 (PP3; 10 microM).


RESULTS
Responses to PE were reduced by use of Y-27632 in laminar vessels (approx inhibition, 55%). However, Y-27632 reduced responses to 5-HT to a greater degree in veins than in arteries (approx inhibition of 55% and 35%, respectively). The Y-27632 also reduced responses of laminar veins to ET-1 by approximately 40% but had no effect on maximum responses of laminar arteries to ET-1, although a rightward shift in the concentration response curve was evident. Addition of PP2 reduced responses to PE, 5-HT, and PGF(2) in laminar veins by approximately 40%, 60%, and 65%, respectively, compared with responses after the addition of PP3; PP2 had no effect on responses to ET-1. In laminar arteries, PP2 reduced 5-HT-induced contractions by approximately 50% but did not affect responses to PE or ET-1.


CONCLUSIONS
Results of the study were consistent with activation of Rho-kinase being important during agonist-induced constriction in laminar vessels, activation of srcPTK being an agonist-dependent event, and more prominent roles for Rhokinase and srcPTK in veins than in arteries.
Department of Physiology and Pharmacology, Institute of Comparative Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389, USA.
Tom P
TP
Robertson
James N
JN
Moore
Erik
E
Noschka
Tristan H
TH
Lewis
Stephen J
SJ
Lewis
John F
JF
Peroni
D000577:Amides / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology; D005528:Foot; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors*; D010656:Phenylephrine / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014680:Veins / Q000187:drug effects*; D054460:rho-Associated Kinases; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*
C509621:4-amino-7-phenylpyrazol(3,4-d)pyrimidine; C412373:AG 1879; D000577:Amides; D019332:Endothelin-1; D047908:Intracellular Signaling Peptides and Proteins; D011720:Pyrazoles; D011725:Pyridines; D011743:Pyrimidines; D014662:Vasoconstrictor Agents; C108830:Y 27632; D010656:Phenylephrine; D012701:Serotonin; D019061:src-Family Kinases; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D002118:Calcium