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 subfamilies of MAP kinases, including extracellular signal-regulated kinases (ERKs) and c-Jun NH2-terminal kinases (JNKs), in the heart of stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) aged 5, 8, 14, and 24 weeks. MAP kinases were determined by using in-gel kinase assay. In both the left and right ventricles of WKY, the activities of ERKs (p44ERK and p42ERK) and JNKs (p46JNK and p55JNK) decreased significantly with age, indicating that aging remarkably downregulated cardiac MAP kinase activities. In SHRSP, left ventricular ERK and JNK activities were already significantly higher at the mild hypertensive phase than they were in the same age of WKY, and they remained higher until development of left ventricular hypertrophy. On the contrary, the right ventricle of SHRSP, which did not exhibit cardiac hypertrophy, had no significant increase in ERK or JNK activities compared with WKY, except for the slight increase in p55JNK in 24-week-old SHRSP. Antihypertensive treatment of SHRSP with imidapril, an angiotensin-converting enzyme inhibitor, decreased the left ventricular JNK activities (P<.01) but did not affect ERK activities, suggesting the contribution of hypertension or the renin-angiotensin system to the increase in JNKs. Our observations provide the first evidence that both ERK and JNK activities are higher in the left ventricle of SHRSP than WKY. However, further study is needed to elucidate the mechanism and the significance of the increased cardiac MAP kinases in SHRSP.
Izumi
Y
Y
Department of Pharmacology, Osaka City University Medical School, Abeno, Osaka, Japan.
Kim
S
S
Murakami
T
T
Yamanaka
S
S
Iwao
H
H
D000375:Aging / Q000378:metabolism* / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D006332:Cardiomegaly / Q000378:metabolism; D002561:Cerebrovascular Disorders; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D009206:Myocardium / Q000201:enzymology*; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY
D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; C065166:imidapril; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases