Differential ANG II-induced growth activation pathways in mesenteric artery smooth muscle cells from SHR

El Mabrouk, M., Touyz, R.M. and Schiffrin, E.L. (2001) Differential ANG II-induced growth activation pathways in mesenteric artery smooth muscle cells from SHR. American Journal of Physiology: Heart and Circulatory Physiology, 281(1), H30-H39.

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Publisher's URL: http://ajpheart.physiology.org/content/281/1/H30.full


Angiotensin II-induced growth signaling mechanisms were investigated in vascular smooth muscle cells (VSMCs) from mesenteric arteries of spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY). In WKY, angiotensin II significantly increased protein synthesis ([(3)H]leucine incorporation) but not DNA synthesis ([(3)H]thymidine incorporation). In SHR, angiotensin II increased protein and DNA synthesis. VSMCs from both strains expressed angiotensin type 1 (AT(1)) and type 2 (AT(2)) receptors. Losartan (an AT(1) receptor antagonist) but not PD-123319 (an AT(2) receptor antagonist) attenuated angiotensin II-stimulated protein synthesis in WKY VSMCs. In SHR, losartan and PD-123319 partially inhibited angiotensin II-induced VSMC proliferation. The mitogen-activated protein kinase or extracellular signal-regulated protein kinase (ERK) kinase inhibitor PD-98059 blocked VSMC growth responses to angiotensin II in both strains. Angiotensin II increased ERK1/2 activation more in SHR than WKY, an effect inhibited by losartan but not PD-123319. LY-294002 [a phosphatidylinositol-3 (PI3) kinase inhibitor] blocked angiotensin II-stimulated ERK1/2 activation in SHR but not in WKY, whereas bisindolylmaleimide [a protein kinase C (PKC) inhibitor] was ineffective. In conclusion, angiotensin II stimulates VSMC proliferation via AT(1) and AT(2) receptors in SHR. In WKY, angiotensin II induces VSMC hypertrophy via AT(1) receptors. ERK1/2-dependent pathways regulated by intracellular Ca(2+) but not PKC mediate these effects. In SHR VSMCs, PI3 kinase plays a role in augmented angiotensin II-induced ERK1/2 phosphorylation. These angiotensin II-mediated signaling events could contribute to vascular remodeling in SHR.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Touyz, Professor Rhian
Authors: El Mabrouk, M., Touyz, R.M., and Schiffrin, E.L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:American Journal of Physiology: Heart and Circulatory Physiology
Journal Abbr.:AJP: Heart and Circulatory Physiology
ISSN (Online):1522-1539

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