Background: Endothelial dysfunction is an initial step for atherosclerotic cardiovascular
disease and highly prevalent in high-risk patients, such as those with hypertension or chronic kidney
disease. Decreased nitric oxide production and/or impaired bioavailability are involved in endothelial
dysfunction. Since blood pressure lowering significantly reduces the risk for future cardiovascular
events in hypertensive patients, several guidelines recommended combination of anti-hypertensive
drugs that had complimentary mode of actions for the treatment of patients with moderate or severe
hypertension. However, effects of combination therapy on nitric oxide generation by endothelial cells
are not fully understood.
Methods: In this study, we examined the effects of amlodipine, a calcium channel blocker, and
irbesartan, an angiotensin II type 1 receptor blocker on nitrate/nitrite generation in angiotensin IIexposed
human umbilical vein endothelial cells. Compared with control, angiotensin II at 100 nM
significantly increased reactive oxygen species generation and reduced mRNA levels of endothelial
nitric oxide synthase in endothelial cells, both of which were prevented by 10 nM irbesartan, but not
1 nM amlodipine. Combination of irbesartan with amlodipine further ameliorated the deleterious
effects of angiotensin II on endothelial cells. Moreover, although amlodipine or irbesartan treatment
alone did not increase nitrate/nitrite generation, combination therapy significantly restored the
decreased nitrate/nitrite production by angiotensin II-exposed endothelial cells.
Results and Conclusion: The present study suggests that combination of irbesartan with amlodipine
could be beneficial against endothelial dysfunction, whose effects may partly be independent on its
blood pressure-lowering properties.