Role of Inducible Nitric Oxide Synthase in Age-Dependent Cardiovascular Depression by Propofol in Rats

Propofol causes systemic hypotension in clinical practice, especially in aged patients. Although various mechanisms are considered as causes of propofol-induced cardiovascular depression in relation to the aging process, changes in the inducible NOS activity in the cardiovascular system remains undefined. We hypothesized that propofol-induced cardiovascular depression is age-dependent, which may be associated with upregulation of inducible nitric oxide synthase (iNOS). The systemic arterial pressure (SAP) and heart rate (HR) of young adult and aged, male Sprague-Dawley rats will be subjected to HR variability analysis during the infusion of propofol at 30 mg/kg per hour. Blood will be collected at baseline and 15 min, 30 min, 60 min, 90 min, 120 min, 180 min and 240 min after propofol infusion for the measurement of propofol concentration using HPLC. Each group will be intravenously given a selective iNOS inhibitor, (S)-methylisothiourea, SMT, 10 , 50 and 250 mmol/kg before the propofol infusion. At the conclusion of the propofol infusion, the thoracic aorta and left ventricle will be harvested, and will be proceeded for the changes in iNOS protein and mRNA using Western blot and real-time PCR techniques. The result of this study will provide the mechanisms of age-dependent cardiovascular depression induced by propofol infusion in relationship to the expression of inducible nitric oxide synthase.

Project ID:PC9408-0705
External Project ID:NSC94-2314-B182-073