Shear Stress Induction of C-type Natriuretic Peptide (CNP) in Endothelial Cells is Independent of NO Autocrine Signaling
0303 health sciences
Anti-Inflammatory Agents
Hemodynamics
Radioimmunoassay
Natriuretic Peptide, C-Type
Free Radical Scavengers
In Vitro Techniques
Blotting, Northern
Nitric Oxide
Dexamethasone
Autocrine Communication
03 medical and health sciences
NG-Nitroarginine Methyl Ester
Animals
Calcium
Cattle
Endothelium, Vascular
RNA, Messenger
Egtazic Acid
Aorta
Cells, Cultured
Chelating Agents
DOI:
10.1114/1.203
Publication Date:
2002-07-27T05:00:49Z
AUTHORS (3)
ABSTRACT
C-type natriuretic peptide (CNP) is secreted by endothelial cells and has vasodilatory and antiproliferative activity against smooth muscle cells. Using defined laminar shear stress exposures of cultured bovine aortic endothelial cells, we investigated the regulation of CNP gene by PhosphorImaging the ratio of CNP mRNA to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA. A 6 h exposure to arterial shear stress of 25 dyn/cm2 caused a marked elevation (10.5 +/- 6.2-fold: n=10, p<0.001) of CNP/GAPDH mRNA ratio compared to stationary controls. Arterial shear stress was 2.6 times more potent than a venous level of shear stress of 4 dyn/cm2 in elevating the CNP/GAPDH mRNA ratio. After 6 h, CNP secretion by shear stressed BAEC was elevated over stationary controls by 3.1-fold (n=5, p<0.001) to a level of 34 +/- 7.5 pg/cm2 BAEC. Shear stress elevated CNP mRNA in the presence of L-NAME (400 microM) indicating that autocrine signaling through shear-induced NO production or guanylate cyclase activation was not involved. Similarly, the tyrosine kinase inhibitor genistein (10 microM), which can also block shear-induced NO production, had no effect on CNP mRNA induction by shear stress in BAEC. The intracellular calcium chelator BAPTA/AM (5 microM) attenuated the shear stress-induced CNP mRNA expression by 71%. Interestingly, dexamethasone (1 microM) potentiated by 2-fold the shear stress enhancement of CNP mRNA. Shear stress was a more potent inducer of CNP than either phorbol myristrate acetate or lipopolysaccharide. Hemodynamic shear stress may be an important physiological regulator of CNP expression with consequent effects on vasodilation and regulation of intimal hyperplasia.
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