July 1, 1999

Angiotensin II stimulates DNA and protein synthesis in vascular smooth muscle cells from human arteries

Structured PICO

Population

Cultured vascular smooth muscle cells derived from resistance arteries (< 300 microm diameter) from subcutaneous gluteal biopsies of healthy subjects (n = 6) and human aortic vascular smooth muscle cells (studied between passages 3 and 6).

Intervention

Angiotensin II (10(-12) - 10(-6) mol/l), evaluated in the absence and presence of losartan (10(-5) mol/l), PD123319 (10(-5) mol/l), or PD98059 (10(-5) mol/l).

Comparator

Control (untreated cells) and endothelin-1.

Outcome

Vascular smooth muscle cell hyperplasia (DNA synthesis measured by 3H-thymidine incorporation) and cell hypertrophy (protein synthesis measured by 3H-leucine incorporation).surrogate

Angiotensin II stimulates hyperplasia and hypertrophy in human vascular smooth muscle cells via AT1 receptor-mediated, ERK-dependent signaling pathways.

Abstract

OBJECTIVE: This study investigates the growth effects and associated signaling pathways of angiotensin II (Ang II) in human vascular smooth muscle cells. METHODS: Cultured vascular smooth muscle cells derived from resistance arteries ( 10(-7) mol/l), where it had a weak stimulatory effect Losartan, but not PD123319, blocked Ang II-stimulated growth responses. Ang II significantly increased phosphorylation of ERK-1 and ERK-2, with maximum responses obtained at 5 min. PD98059 inhibited Ang II-stimulated ERK activity and abrogated agonist-induced DNA and protein synthesis. Losartan, but not PD123319 inhibited Ang II-induced phosphorylation of ERK-1 and ERK-2. CONCLUSIONS: Ang II stimulates both hyperplasia and hypertrophy in vascular smooth muscle cells from human arteries. These growth effects are mediated via Ang II receptors of the AT1 subtype that are linked to ERK-dependent signaling pathways.

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Cite This Study

Touyz et al. (Thu,) studied this question.

synapsesocial.com/papers/6a200937d5e8712fdf65b93f https://doi.org/https://doi.org/10.1097/00004872-199917070-00006

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