It is well known that blood pressure could be increased with age and hypertension is a public health problem that affects.25% of the adult population worldwide. Hypertension has been identified as the leading risk factor for mortality and ranks as the third-leading cause of disability-adjusted life-years. Despite the availability of numerous antihypertensive agents, current antihypertensive treatment does not always provide sufficient BP control and cardiovascular protection. The combination therapy with two or more classes of antihypertensive agents is a strategy adopted for improving BP control and cardiovascular protection, which has been suggested in recent guidelines even as an initial therapeutic option. Among the various classes of antihypertensive medications currently available, calcium channel blockers including amlodipine are one of the most popular first-line treatments including that for aged people. Though widely prescribed in high-risk and aged patients with Fingolimod multiple risk factors, the use of high-dose CCBs such as AM may be limited due to its relatively less vascular protection in comparison with other antihypertensives. Recent clinical trials suggested that the combination of low-dose CCBs and other medications with particular vascular protective effects might be an attractive alternative strategy especially for elderly hypertension. It has been shown in both preclinical and clinical studies that during the development of hypertension, the production of superoxide anion derived from NAD H oxidase could be increased with age, which may counteract the enhanced nitric oxide production derived from inducible NO synthase and generate vasoconstrictor responses on aorta. It is then possible that the inhibition of vascular NAD H oxidase may help to improve BP control as well as vascular protection in the presence of hypertension. Dextromethorphan is a dextrorotatory morphinan, which has been widely used as a nonopioid cough suppressant for decades though the exact mechanisms are not clarified. Interestingly, previous studies using animal models of cerebral ischemia and hypoglycemic neural injuries have demonstrated the neuroprotective activity of DM, which might be related to its effects on NADPH oxidase since DM may effectively inhibit the production of reactive oxygen species induced by 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine. However, it was not known whether DM may provide additional cardiovascular protection to hypertension. Accordingly, this study was conducted to test the hypothesis that DM by inhibiting vascular NADPH oxidase may improve BP control and enhance vascular protection in aged hypertensive animals with or without GDC-0449 standard antihypertensive treatment such as AM.