This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hishikawa, K. Articles by Lüscher, T. F. Search for Related Content PubMed PubMed Citation Articles by Hishikawa, K. Articles by Lüscher, T. F. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB GLUCOSE NITRIC OXIDE

(Hypertension. 1998;32:1011-1015.)
© 1998 American Heart Association, Inc.

Scientific Contributions

Felodipine Inhibits Free-Radical Production by Cytokines and Glucose in Human Smooth Muscle Cells

Keiichi Hishikawa; Thomas F. Lüscher

From the Cardiology Division and Institute of Clinical Pharmacology, University Hospitals, Bern and Zürich, and Cardiovascular Research, Institute of Physiology, University Zürich, Switzerland.

Correspondence to Dr Thomas F. Lüscher, University Hospital, CH-8091 Zürich, Switzerland.

Abstract—An imbalance between nitric oxide (NO) and superoxide is importantly involved in the pathogenesis of vascular disease. Inflammatory stimuli and risk factors contribute to these alterations. Calcium antagonists and angiotensin-converting enzyme inhibitors are commonly used cardiovascular drugs. To clarify the effect of felodipine and ramiprilat on the balance of these free radicals, we stimulated human aortic smooth muscle cells (HASCs) with cytokines (human interleukin-1ß, tumor necrosis factor-, lipopolysaccharide, and/or interferon-) or high glucose in the presence and absence of these compounds. Felodipine, but not ramiprilat, concentration-dependently inhibited cytokine-induced NO production and NO synthase (NOS) mRNA induction. The antioxidant N-acetylcysteine also inhibited cytokine-induced NO production and induction of inducible NOS mRNA. Moreover, felodipine inhibited cytokine-induced superoxide production both in the presence and absence of an NOS inhibitor, suggesting that it acted as a superoxide scavenger and not as an inhibitor of inducible NOS induction. High glucose treatment (22 mmol/L for 48 hours) also significantly increased superoxide production in HASCs, and this increase was inhibited in a concentration-dependent manner by felodipine but not by ramiprilat. These results suggest that felodipine may exert vascular protective effects by suppressing free radical generation in human smooth muscle cells during activation of inflammatory mechanisms and diabetic conditions.

Key Words: nitric oxide • free radicals • superoxides • cytokines • glucose

This article has been cited by other articles:

				J. D. Dietz, S. Du, C. W. Bolten, M. A. Payne, C. Xia, J. R. Blinn, J. W. Funder, and X. Hu A Number of Marketed Dihydropyridine Calcium Channel Blockers Have Mineralocorticoid Receptor Antagonist Activity Hypertension, March 1, 2008; 51(3): 742 - 748. [Abstract] [Full Text] [PDF]

				V. Gerzanich, S. Ivanova, M. S. van der Heijden, H. Zhou, and J. M. Simard Trans-Cellular Proliferating Cell Nuclear Antigen Gene Activation in Cerebral Vascular Smooth Muscle by Endothelial Oxidative Injury In Vivo Arterioscler Thromb Vasc Biol, November 1, 2003; 23(11): 2048 - 2054. [Abstract] [Full Text] [PDF]

				K. Hishikawa, B. S. Oemar, F. C. Tanner, T. Nakaki, T. Fujii, and T. F. Luscher Overexpression of Connective Tissue Growth Factor Gene Induces Apoptosis in Human Aortic Smooth Muscle Cells Circulation, November 16, 1999; 100(20): 2108 - 2112. [Abstract] [Full Text] [PDF]

				J. E. Toblli, L. Ferder, M. Angerosa, and F. Inserra Effects of Amlodipine on Tubulointerstitial Lesions in Normotensive Hyperoxaluric Rats Hypertension, October 1, 1999; 34(4): 854 - 858. [Abstract] [Full Text] [PDF]