ENDOTHELIN‐INDUCED ACTIVATION OF MITOGEN‐ACTIVATED PROTEIN KINASES IN GLOMERULAR MESANGIAL CELLS FROM NORMOTENSIVE AND STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS

1. Kinase assay in myelin basic protein (MBP) containing polyacrylamide gels revealed that endothelin‐1 (ET‐1) and ET‐3 increased MBP kinase activities in glomerular mesangial cells (MC) from Wistar‐Kyoto (WKY) rats and spontaneously hypertensive rat (SHRSP). ET‐1 stimulated MBP kinase activities more potently than ET‐3. 2. Immunoprecipitation with anti‐41‐kDa MAPK antiserum showed that the MBP kinases activated by ET‐1 correspond to 43‐ and 41‐kDa MAPK. 3. Since Phorbol 12‐myristate 13‐acetate, a direct activator of protein kinase C, also activated MAPK, protein kinase C was suggested to mediate ET‐induced activation of MAPK. 4. These results suggest that MAPK may mediate the ET actions in glomerular mesangial cells from normotensive rats as well as spontaneously hypertensive rats. Since ET is produced by vascular endothelial cells of the kidney and glomerular mesangial cells, the ET signalling pathway may have some physiological and pathophysiological significance in wivo glomerulus.