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.
Robertson
Tom P
TP
Department of Physiology and Pharmacology, Institute of Comparative Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389, USA.
Moore
James N
JN
Noschka
Erik
E
Lewis
Tristan H
TH
Lewis
Stephen J
SJ
Peroni
John F
JF
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