Journal
JOURNAL OF HYPERTENSION
Volume 19, Issue 3, Pages 553-559Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00004872-200103001-00006
Keywords
MAP kinases; angiotensin II receptors; tyrosine kinases; irbesartan; PD123319; hypertension; small arteries
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Objectives The present study investigates effects of angiotensin II on activation of extracellular signal-regulated protein kinase (ERK)1/2, p38 mitogen activated-protein kinase (p38MAPK) and c-Jun amino terminal kinase (JNK) in vascular smooth muscle cells from spontaneously hypertensive rats (SHR), Methods Vascular smooth muscle cells (VSMC) from mesenteric arteries of Wistar- Kyoto (WKY) rats and SHR were studied. Angiotensin II-induced phosphorylation of ERK1/2, JNK and p38MAPK were assessed by Western blot analysis. c-fos mRNA expression by angiotensin II was determined by reverse transcriptase-polymerase chain reaction in the absence and presence of PD98059, selective inhibitor of ERK1/2-dependent pathways and S8202190, selective p38MAPK inhibitor. Results Angiotensin II increased phosphorylation of ERK1/2 and p38MAPK, but not JNK. Responses were significantly increased in SHR compared with WKY, Irbesartan, AT(1) receptor antagonist, but not PD123319, AT(2) receptor blocker, abolished angiotensin Ii-induced effects. PP2, selective Src inhibitor, decreased angiotensin II-mediated activation of MAP kinases, Angiotensin II increased c-fos mRNA expression in SHR and had a small stimulatory effect in WKY. These actions were inhibited by PD98059, whereas S8202190 had no effect. Conclusions Angiotensin II-induced activation of vascular ERK1/2 and p38MAPK is increased in SHR, These effects are mediated via AT(1) receptors, which activate Src-dependent pathways. Overexpression of c-fos mRNA in SHR is due to ERK1/2-dependent, p38MAPK-independent pathways. Our results suggest that angiotensin II activates numerous MAP kinases in VSMCs and that differential activation of these kinases may be important in altered growth signaling in VSMCs from SHR.
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