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 response to shear stress. Levels of vasoactive peptides such as adrenomedullin (AM), endothelin-1 (ET-1), C-type natriuretic peptide (CNP), and nitric oxide (NO) are affected by fluid shear stress. AM, a potent vasodilator and suppressor of smooth muscle cell proliferation, contains the shear stress responsive element (SSRE) "GAGACC" in its promoter region. To examine the role of AM in the shear stress response, cultured human aortic endothelial cells (HAoECs) were exposed to fluid shear stresses of 12 and 24 dynes/cm2 in a cone-plate shear stress loading apparatus for various time periods, and the levels of AM gene expression and peptide secretion from HAoECs were measured by Northern blotting analysis and radioimmunoassay (RIA), respectively. Both AM gene transcription and AM peptide levels were down-regulated by fluid shear stress in a time- and magnitude-dependent manner. Our results demonstrate that the normal level of arterial shear stress down-regulates AM expression in HAoECs, suggesting that AM participates in the modulation of vascular tone by fluid shear stress.