CARDIAC MITOGEN-ACTIVATED PROTEIN-KINASE ACTIVITIES ARE CHRONICALLY INCREASED IN STROKE-PRONE HYPERTENSIVE RATS

To examine chronic changes in mitogen-activated protein (MAP) kinases in cardiac hypertrophy, we determined the activities of two subfamilie s of MAP kinases, including extracellular signal-regulated kinases (ER Ks) and c-Jun NH2-terminal kinases [JNKs], in the heart of stroke-pron e spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats WKY) a ged 5, 8, 14, and 24 weeks. MAP kinases were determined by using in-ge l kinase assay. In both the left and right ventricles of WKY, the acti vities of ERKs (p44ERK and p42ERK) and JNKs (p46JNK and p55JNK) decrea sed significantly with age, indicating that aging remarkably downregul ated cardiac MAP kinase activities. In SHRSP, left ventricular ERK and JNK activities were already significantly higher at the mild hyperten sive phase than they were in the same age of WKY, and they remained hi gher until development of left ventricular hypertrophy. On the contrar y, the right ventricle of SHRSP, which did not exhibit cardiac hypertr ophy, had no significant increase in ERK or JNK activities compared wi th WKY, except for the slight increase in p55JNK in 24-week-old SHRSP. Antihypertensive treatment of SHRSP with imidapril, an angiotensin-co nverting enzyme inhibitor, decreased the left ventricular JNK activiti es (P<.01) but did not affect ERK activities, suggesting the contribut ion of hypertension or the renin-angiotensin system to the increase in JNKs. Our observations provide the first evidence that both ERK and J NK activities are higher in the left ventricle of SHRSP than WKY. Howe ver, further study is needed to elucidate the mechanism and the signif icance of the increased cardiac MAP kinases in SHRSP.