Endothelin modulates angiotensin II-induced mitogenesis of human mesangial cells

Bakris, G.L.; Re, R.N.

American Journal of Physiology 264(6 Pt 2): F937-F942


ISSN/ISBN: 0002-9513
PMID: 8322895
Accession: 008604816

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Angiotensin II (ANG II) elicits either a hypertrophic or hyperplastic response depending on culture conditions. Human mesangial cell (HMC)-generated endothelin (ET) plays a role in mediating the hyperplastic effects of arginine vasopressin. The interaction between ANG II and ET is not described in HMC. The present study evaluates the possible effect of ANG II on HMC production of ET, its relationship to mitogenesis, and the effect of insulin. ANG II (10-8 M) increased (3H)thymidine incorporation in proliferative HMC at 48 h (13 +- 1 vs. 24 +- 1 times 103 counts cntdot min-1 cntdot well-1, for control vs. ANG II; P lt 0.05). Cell counts showed parallel increases (12 +- 1 (control) vs. 18 +- 1 times 10-3 counts/well; P lt 0.05). This mitogenic effect was attenuated by a monoclonal antibody to ET-1 or the ANG II-receptor antagonist, DuP 753. Insulin potentiated the mitogenic response of ANG II through increases in HMC ET production (69 +- 7 vs. 189 +- 13 pg/ml, for insulin alone vs. insulin + ANG II; P lt 0.05). This study supports the concept that ANG II may act as a mitogen under certain culture conditions and its effect is, in part, mediated through ET.