Stretch induces mitogen-activated protein kinase activation and myogenic tone through 2 distinct pathways

The aim of this study was to evaluate the involvement of the mitogen-activa ted protein kinase (ERK1/2) pathway in response to stretch in a blood vesse l developing myogenic tone on stretch. Indeed, in resistance arteries and v eins, the main effect of pressure is to induce a maintained vasoconstrictor (myogenic) tone. Isolated segments of rabbit facial vein were mounted in o rgan baths and submitted to isometric stretch. In this experimental model, myogenic tone was absent when the bath temperature was 33 degrees C. ERK1/2 activity was determined in each isolated segment by an in-gel kinase assay . Wall tension and ERK1/2 activity were measured in the same samples in the presence (39 degrees C) or in the absence of myogenic tone (33 degrees C). At 39 degrees C, a 5-mN wall tension induced myogenic tone (5.7+/-1.8 mN) and an increase in ERK1/2 activity (282+/-52% versus unstretched vessels, P <0.05). At 33 degrees C, in the absence of myogenic tone, ERK1/2 activity w as similarly increased by stretch (254+/-35% versus unstretched vessels). T he calcium-dependent and -independent protein kinase C (PKC) blocker Ro-31- 8220 (5 x 10(-7) mol/L), but not the calcium-dependent PKC blocker Go-6976 (10(-6) mol/L), inhibited myogenic tone. However, ERK1/2 activity was not a ffected by either PKC blocker. Genistein (10(-7) mol/L), a general tyrosine kinase inhibitor, but not herbimycin A (5 x 10(-7) mol/L), a cSrc-family t yrosine kinase inhibitor, suppressed stretch-induced ERK1/2 activation (P<0 .05) without affecting myogenic tone. Nifedipine (10(-6) mol/L), a voltage- dependent calcium entry inhibitor, and ryanodine (10(-6) mol/L), which depl etes calcium stores, both inhibited ERK1/2 activity (113+/-12% and 121+/-7% , respectively; P<0.05) without affecting myogenic tone. The mitogen-activa ted protein kinase kinase inhibitor PD 98059 (5 x 10(-6) mol/L) also inhibi ted ERK1/2 activation without affecting myogenic tone. The present results suggest that stretching the rabbit facial vein induced 2 distinct pathways, one leading to myogenic tone (via a non-calcium-dependent PKC activation) and one leading to ERK1/2 activation through a calcium-dependent pathway in volving tyrosine kinase.