Role of aortic nitric oxide synthase 3 (eNOS) in the systemic vasodilation of portal hypertension

Background & Aims: In portal hypertension, the mechanisms responsible for nitric oxide (NO) overproduction and vasodilation have not yet been clearly identified. One hypothesis is that NO synthase (NOS) 3 is overactivated because of shear stress in endothelial cells caused by hyperkinetic circulation. The aim of this study was to evaluate aortic NOS3 after a reduction of blood flow by long-time β-adrenoceptor antagonist administration. Methods: Propranolol or atenolol was administered by gavage in portal vein–stenosed and sham-operated rats. The vascular reactivity of thoracic aortic rings to phenylephrine, total aortic NOS activity, and aortic NOS3 messenger RNA and protein expressions were studied. Results: After propranolol or atenolol administration, the aortic hyporesponse returned to normal in portal vein–stenosed rats. Total aortic NOS activity was higher in portal vein–stenosed aortas and significantly decreased after β-blocker administration. Aortic NOS3 expressions were more marked in portal vein–stenosed aortas than in controls, but NOS3 expressions were reduced after propranolol administration. Conclusions: In portal hypertension, aortic NOS3 activity and expressions are enhanced but return to normal after β-blocker administration. These results suggest that in portal hypertension, increased shear stress, related to high blood flow, induces enhanced aortic NOS3. GASTROENTEROLOGY 2000;119:196-200