Acute hypertension activates mitogen-activated protein kinases in arterial wall.
Mitogen-activated protein (MAP) kinases are rapidly activated in cells stimulated with various extracellular signals by dual phosphorylation of tyrosine and threonine residues. They are thought to play a pivotal role in transmitting transmembrane signals required for cell growth and differentiation. Herein we provide evidence that two distinct classes of MAP kinases, the extracellular signal-regulated kinases (ERK) and the c-Jun NH2-terminal kinases (JNK), are transiently activated in rat arteries (aorta, carotid and femoral arteries) in response to an acute elevation in blood pressure induced by either restraint or administration of hypertensive agents (i.e., phenylephrine and angiotensin II). Kinase activation is followed by an increase in c-fos and c-jun gene expression and enhanced activating protein 1 (AP-1) DNA-binding activity. Activation of ERK and JNK could contribute to smooth muscle cell hypertrophy/hyperplasia during arterial remodeling due to frequent and/or persistent elevations in blood pressure.
Xu
Q
Q
Section on Gene Expression and Aging, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
Liu
Y
Y
Gorospe
M
M
Udelsman
R
R
Holbrook
N J
NJ
D000208:Acute Disease; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta; D001483:Base Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D004789:Enzyme Activation; D015870:Gene Expression; D016762:Genes, fos; D016758:Genes, jun; D006973:Hypertension / Q000201:enzymology*; D048031:JNK Mitogen-Activated Protein Kinases; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D010656:Phenylephrine / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015854:Up-Regulation
D017931:DNA Primers; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D000804:Angiotensin II; D010656:Phenylephrine; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases