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. Sample Population - Laminar arteries and veins obtained from 13 adult mixed-breed horses. Procedures - Laminar vessels were mounted on myographs and exposed to phenylephrine (PE), 5-hydroxytryptamine (5-HT), prostaglandin F_2α (PGF_2α,), and endothelin-1 (ET-1) with or without the Rho-kinase inhibitor Y-27632 (10μM), srcPTK inhibitor PP2 (10μM), or a negative control analogue for PP2 (PP3; 10μM). 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_2α 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 and Clinical Relevance - 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 Rho-kinase and srcPTK in veins than in arteries.