SHEAR-STRESS DOWN-REGULATES GENE-TRANSCRIPTION AND PRODUCTION OF ADRENOMEDULLIN IN HUMAN AORTIC ENDOTHELIAL-CELLS

Vascular endothelial cells are potent modulators of vascular tone in r esponse to shear stress. Levels of vasoactive peptides such as adrenom edullin (AM), endothelin-1 (ET-1), C-type natriuretic peptide (CNP), a nd nitric oxide (NO) are affected by fluid shear stress. AM, a potent vasodilator and suppressor of smooth muscle cell proliferation, contai ns the shear stress responsive element (SSRE) ''GAGACC'' in its promot er region. To examine the role of AM in the shear stress response, cul tured human aortic endothelial cells (HAoECs) were exposed to fluid sh eer stresses of 12 and 24 dynes/cm(2) in a cone-plate shear stress loa ding apparatus for various time periods, and the levels of AM gene exp ression and peptide secretion from HAoECs were measured by Northern bl otting analysis and radioimmunoassay (RIA), respectively. Both AM gene transcription and AM peptide levels were down-regulated by fluid shea r stress in a time- and magnitude-dependent manner. Our results demons trate that the normal level of arterial shear stress down-regulates AM expression in HAoECs, suggesting that AM participates in the modulati on of vascular tone by fluid shear stress. (C) 1998 Wiley-Liss, Inc.