Abstract
Dihydropiridine calcium channel blocker nifedipine restores nitric oxide-mediated vasodilation in human hypertension. The mechanims involved have not been fully characterized but may relate to endothelial protection. Mechanical forces such as pulsatile stretch are involved in superoxide anion production. To clarify the effect of nifedipine on the balance between nitric oxide and superoxide anion, human cultured aortic endothelial cells were exposed to pulsatile stretch in the presence and in the absence of this compound. Rhytmic stretching was given for 1 hour by a computerized Flexercell strain unit (10% average elongation, 50 cycles per minute). Superoxide anion production was measured as the superoxide dismutase-inhibitable reduction of cytochrome c. Stretch-induced production of superoxide anion was inhibited in a concentration-dependent manner by nifedipine [6.2±0.9 vs 2.1±0.6* and 4.8±0.4*, 2.4±0.5* nmol/60 min/105 cells for stretch vs control and stetch plus nifedipine (10−7 and 10−6 M), respectively; n=6; *P<0.05 vs stretch]. This antioxidant activity of nifedipine may exert vascular protective effects in human endothelial cells. Thus, nifedipine may affect mechanical forces which, as determinants of the balance between nitric oxide and superoxide anion, are likely to play a key role in the pathophysiology of hypertensive vascular disease
Cosentino, F