SHEAR-STRESS AUGMENTS EXPRESSION OF C-TYPE NATRIURETIC PEPTIDE AND ADRENOMEDULLIN

Shear stress is known to dilate blood vessels and exert antiproliferat ive effects on vascular walls; these effects have been ascribed to she ar stress-induced upregulation of endothelium-derived vasoactive subst ances, mainly nitric oxide and prostacyclin. We have demonstrated the significance of C-type natriuretic peptide (CNP) as a novel endotheliu m-derived relaxing peptide (EDRP) that shares a cGMP pathway with nitr ic oxide. Adrenomedullin is a recently isolated EDRP that elevates int racellular cAMP as prostacyclin does. To elucidate the possible role o f these EDRPs under shear stress, we examined the effect of physiologi cal shear stress on CNP mRNA expression in endothelial cells derived f rom the human umbilical vein (HUVECs), bovine aorta (BAECs), and murin e lymph nodes (MLECs) as well as adrenomedullin mRNA expression in HUV ECs. CNP mRNA was stimulated prominently in HUVECs under shear stress of 15 dyne/cm(2) in a time-dependent manner (4 hours, sixfold increase compared with that in the static condition; 24 hours, 30-fold increas e). Similar results were obtained in BAECs (4 hours, twofold increase; 24 hours, threefold increase) and MLECs (4 hours, threefold increase; 24 hours, 10-fold increase). Augmentation of CNP mRNA expression that was dependent on shear stress intensity was also observed (5 dyne/cm( 2), 2.5-fold increase of static; 15 dyne/cm(2), 4.5-fold increase). In creased CNP secretion was also confirmed by the specific radioimmunoas say for CNP. Adrenomedullin mRNA expression in HUVECs increased under shear stress of 15 dyne/cm(2) in a time-dependent manner (4 hours, 1.2 -fold increase of static; 24 hours, threefold increase) and shear stre ss intensity-dependent manner (15 dyne/cm(2), threefold increase compa red with that at 5 dyne/cm(2)). These results suggest that the coordin ated augmentation of mRNA expression of these novel EDRPs may constitu te shear stress-dependent vasodilator and antiproliferative effects.