Endothelin-1 and angiotensin-II stimulate delayed mitogenesis in cultured rat aortic smooth muscle cells: Evidence for common signaling mechanisms

Helen Weber, Maria L. Webb, Randy Serafino, David S. Taylor, Suzanne Moreland, Jon Norman, Christopher J. Molloy

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

The vasoactive peptides endothelin-1 (ET-1) and angiotensin-II (AII) have been implicated in chronic hypertension and may play important roles in related vascular diseases such as restenosis and atherosclerosis. Using a rat aortic smooth muscle (RASM) cell model, both ET-1 and AII induced concentration-dependent delayed increases in DNA synthesis relative to that in the serum-deprived controls. Stimulation of DNA synthesis was maximal at 100 nM for each peptide. AII treatment of RASM cells resulted in a greater mitogenic effect (4- to 7-fold) than that observed for ET-1 (3-fold). When added in the presence of AII, ET-1 had a supplemental effect on DNA synthesis (5- to 10-fold above control). Although RASM cells expressed both ET(A) and AT1 receptors, radioligand binding experiments indicated that approximately 10-fold as many AT1 receptors as ET(A) receptors were present. In signal transduction studies, ET-1 and AII each elicited concentration-dependent increases in the intracellular Ca2+ concentration. ET-1 and AII also stimulated phosphoinositide metabolism and phosphorylation of a specific substrate for protein kinase-C. The release of total inositol phosphates in response to ET-1 and AII was concentration dependent and inhibited by the ET(A) receptor-selective antagonist BQ-123 and the AT1 receptor-selective antagonist losartan, respectively. In addition, tyrosine phosphorylation of 120- and 75-kilodalton proteins as well as the mitogen-activated protein kinases p44(mapk) and p42(mapk) was observed within 5 min of the addition of either ET-1 or AII. Taken together, these data indicate that ET-1 and AII may promote smooth muscle cell growth through common intracellular signaling mechanisms.

Original languageEnglish (US)
Pages (from-to)148-158
Number of pages11
JournalMolecular Endocrinology
Volume8
Issue number2
DOIs
StatePublished - Feb 1 1994
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Endocrinology

Fingerprint Dive into the research topics of 'Endothelin-1 and angiotensin-II stimulate delayed mitogenesis in cultured rat aortic smooth muscle cells: Evidence for common signaling mechanisms'. Together they form a unique fingerprint.

  • Cite this