Estrogen activates phosphatases and antagonizes growth-promoting effect of angiotensin II

65Citations
Citations of this article
12Readers
Mendeley users who have this article in their library.

Abstract

Accumulating evidence suggests that estrogen exerts cardioprotective effects and protects against neointima formation in response to vascular injury in vivo, whereas angiotensin (Ang) II stimulation via the Ang II type 1 (AT1 receptor exaggerates vascular injury. We postulate that estrogen treatment antagonizes the AT1 receptor-mediated growth-promoting effects in vascular smooth muscle cells (VSMCs). The present in vitro study was designed to explore this possibility and to establish the cellular mechanism whereby estrogen attenuates the growth of VSMCs. Primary cultures of VSMCs derived from male adult Sprague-Dawley rats express exclusively AT1 receptors. Treatment with Ang II enhanced proliferation of VSMC and c-fos expression, whereas 17β-estradiol (E2) attenuated these vasotrophic effects of Ang II. We also demonstrated that E2 attenuated AT1 receptor-mediated extracellular signal-regulated kinase activation and that this effect of E2 was restored by pretreatment with vanadate or okadaic acid. Moreover, we demonstrated that E2 enhanced SHP-1 activity, rapidly reaching a peak after 3 minutes of E2 stimulation, whereas E2 transactivated mitogen-activated protein kinase phosphatase-1 expression, showing a peak after 60 minutes of E2 treatment. SHP-1 activation was not influenced by actinomycin D treatment, whereas E2-mediated mitogen-activated protein kinase phosphatase-1 expression was attenuated. Taken together, our results suggest a novel mechanism of vasoprotection by which estrogen antagonizes the effect of the AT1 receptor via the activation and induction of phosphatases through nongenomic as well as genomic signaling.

Cite

CITATION STYLE

APA

Takeda-Matsubara, Y., Nakagami, H., Iwai, M., Cui, T. X., Shiuchi, T., Akishita, M., … Horiuchi, M. (2002). Estrogen activates phosphatases and antagonizes growth-promoting effect of angiotensin II. Hypertension, 39(1), 41–45. https://doi.org/10.1161/hy1201.097197

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free