Temporal regulation of endothelial ET-1 and eNOS expression in intact human conduit vessels exposed to different intraluminal pressure levels at physiological shear stress

Objective: By using a computerized vascular perfusion model, we investigate d temporal effects of sub-acute pressure elevation on vasomotor behavior an d expression of endothelin-1 (ET-1) and endothelial nitric oxide synthase ( eNOS) in intact human conduit vessels. Methods: Paired umbilical veins were perfused during 1.5, 3 and 6 h under high/low intraluminal pressure (40/20 mmHg) and at identical shear stress level of 10 dyn/cm(2). ET-1 and eNOS g ene and protein expression was quantified with real-time reverse-transcribe d polymerase chain reaction and quantitative immunohistochemistry, respecti vely. Results: Pressure induced differential temporal regulation patterns o f ET-1 and eNOS gene expression. During the high pressure condition, eNOS m RNA was upregulated after 3 h and leveled off after 6 h of perfusion, while ET-1 mRNA was elevated after 6 h perfusion. Immunohistochemistry verified synchronal changes at the protein level. Significant vasodilation was obser ved after 3 h in the high-pressure system. Conclusion: Thus, subacute press ure elevation exerts differential effects on the endothelial eNOS/ET-1 expr ession, which dynamically regulate the vasomotor tone. (C) 2000 Elsevier Sc ience B.V. All rights reserved.