Felodipine inhibits free-radical production by cytokines and glucose in human smooth muscle cells

An imbalance between nitric oxide (NO) and superoxide is importantly involv ed in the pathogenesis of vascular disease. Inflammatory stimuli and risk f actors contribute to these alterations. Calcium antagonists and angiotensin -converting enzyme inhibitors are commonly used cardiovascular drugs. To cl arify the effect of felodipine and ramiprilat on the balance of these free radicals, we stimulated human aortic smooth muscle cells (HASCs) with cytok ines (human interleukin-1 beta, tumor necrosis factor-alpha, lipopolysaccha ride, and/or interferon-gamma) or high glucose in the presence and absence of these compounds. Felodipine, but not ramiprilat, concentration-dependent ly inhibited cytokine-induced NO production and NO synthase (NOS) mRNA indu ction. The antioxidant N-acetylcysteine also inhibited cytokine-induced NO production and induction of inducible NOS mRNA. Moreover, felodipine inhibi ted cytokine-induced superoxide production both in the presence and absence of an NOS inhibitor, suggesting that it acted as a superoxide scavenger an d not as an inhibitor of inducible NOS induction. High glucose treatment (2 2 mmol/L for 48 hours) also significantly increased superoxide production i n HASCs, and this increase was inhibited in a concentration-dependent manne r by felodipine but not by ramiprilat. These results suggest that felodipin e may exert vascular protective effects by suppressing free radical generat ion in human smooth muscle cells during activation of inflammatory mechanis ms and diabetic conditions.