CYCLIC STRAIN INCREASES ENDOTHELIAL NITRIC-OXIDE SYNTHASE ACTIVITY

Background. Endothelial nitric oxide synthase (eNOS) is an important e nzyme that controls the production of a potent vascular smooth muscle relaxing factor, nitric oxide. However, the role of hemodynamic forces (blood pressure, cyclic strain, and shear stress) on the regulation o f eNOS has not been fully elucidated. Recently, we showed that cyclic strain increases eNOS gene and protein in cultured bovine aortic endot helial cells (EC). Because an increase in gene transcription and prote in synthesis may not necessarily translate into an increase in functio nal activity, the aim of this study was to determine the effects of cy clic strain on eNOS activity. Methods. EC were seeded onto plates with flexible bottoms that can be deformed by vacuum and were then exposed to 60 cycles/minute of either 24% maximum strain (-20 kPa vacuum) or 10% maximum strain (-5 kPa vacuum) for 24 hours, eNOS activity was ass essed, and nitric oxide production was determined (as nitrite) by the Greiss reaction. Results. Twenty-four percent strain, at 60 cycles/min , but not 10% strain significantly increases eNOS activity compared wi th stationary controls. Both strain regimens increased nitric oxide (a s nitrite) in culture media compared with stationary controls, althoug h nitrite in media of EC exposed to high strain were significantly inc reased compared with the lower strain. Conclusions. Cyclic strain incr eases eNOS activity in cultured bovine aortic EC. These results may in dicate the importance of hemodynamic forces in the regulation of eNOS in vivo.