July 1, 2001

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

Q: What is the clinical evidence from this study?

Study design: Other. Population: Hypertension. Intervention: Angiotensin II vs. Various receptor antagonists and kinase inhibitors. Primary outcome: Protein synthesis, DNA synthesis, and ERK1/2 activation.

Key Result

Angiotensin II stimulates VSMC proliferation via AT1 and AT2 receptors in SHR, whereas it induces hypertrophy via AT1 receptors in WKY rats, mediated by ERK1/2-dependent pathways.

Structured PICO

Population

In vitro study of vascular smooth muscle cells from mesenteric arteries of spontaneously hypertensive and Wistar-Kyoto rats.

Intervention

Angiotensin II (with and without inhibitors: losartan, PD-123319, PD-98059, LY-294002, bisindolylmaleimide)

Comparator

Responses between SHR and WKY strains, and baseline/untreated cells

Outcome

Protein synthesis ([(3)H]leucine incorporation) and DNA synthesis ([(3)H]thymidine incorporation)surrogate

Angiotensin II induces differential growth activation pathways in vascular smooth muscle cells of hypertensive versus normotensive rats, potentially contributing to vascular remodeling.

Abstract

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)Hleucine incorporation) but not DNA synthesis ((3)Hthymidine 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.

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Cite This Study

Mabrouk et al. (Sun,) conducted a other in Hypertension. Angiotensin II vs. Various receptor antagonists and kinase inhibitors was evaluated on Protein synthesis, DNA synthesis, and ERK1/2 activation. Angiotensin II stimulates VSMC proliferation via AT1 and AT2 receptors in SHR, whereas it induces hypertrophy via AT1 receptors in WKY rats, mediated by ERK1/2-dependent pathways.

synapsesocial.com/papers/6a200c86d4e6d3589704dabc https://doi.org/https://doi.org/10.1152/ajpheart.2001.281.1.h30

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