Electron paramagnetic resonance investigation on modulatory effect of benidipine on membrane fluidity of erythrocytes in essential hypertension

• Published in: Heart and vessels Vol. 23; no. 2; pp. 134 - 139
• Main Author: Tsuda, Kazushi
• Format: Journal Article
• Language: English
• Published: Japan Springer Japan 01.03.2008; Springer Nature B.V
• Subjects: Administration, Oral; Aged; Antihypertensive Agents - administration & dosage; Arginine - pharmacology; Biomedical Engineering and Bioengineering; Blood Pressure - drug effects; Blood Viscosity - drug effects; Calcium Channel Blockers - administration & dosage; Cardiac Surgery; Cardiology; Cellular biology; Dihydropyridines - pharmacology; Dose-Response Relationship, Drug; Drug therapy; Electron Spin Resonance Spectroscopy; Erythrocyte Membrane - drug effects; Erythrocytes; Female; Humans; Hypertension; Hypertension - blood; Hypertension - drug therapy; Hypertension - physiopathology; Male; Medicine; Medicine & Public Health; Membrane Fluidity - drug effects; Membranes; Middle Aged; Nitric Oxide - blood; NMR; Nuclear magnetic resonance; Short Communication; Treatment Outcome; Vascular Surgery; Erythrocyte; Hypertension; Membrane fluidity; Electron paramagnetic resonance; Benidipine; Oral administration
• ISSN: 0910-8327; 1615-2573
• DOI: 10.1007/s00380-007-1017-6

It has been shown that benidipine, a long-lasting calcium (Ca) channel blocker, may exert its protective effect against vascular disorders by increasing nitric oxide (NO) production. The purpose of the present study was to investigate whether orally administered benidipine might influence the membrane function in patients with essential hypertension. We measured the membrane fluidity of erythrocytes by using an electron paramagnetic resonance (EPR) and spin-labeling method. In the preliminary study using erythrocytes obtained from healthy volunteers, benidipine decreased the order parameter (S) for 5-nitroxide stearate (5-NS) and the peak height ratio (ho/h-1) for 16-NS in the EPR spectra in vitro. The finding indicated that benidipine increased the membrane fluidity and improved the microviscosity of erythrocytes. In addition, it was demonstrated that the effect of benidipine on membrane fluidity of erythrocytes was significantly potentiated by the NO-substrate, L-arginine. In the separate series of the study, we observed that orally administered benidipine for 4 weeks significantly increased the membrane fluidity of erythrocytes with a concomitant increase in plasma NO metabolite levels in hypertensive subjects. The results of the present study demonstrated that benidipine might increase the membrane fluidity and improve the microviscosity of erythrocytes both in vitro and in vivo, to some extent, by the NO-dependent mechanism. Furthermore, it is strongly suggested that orally administered benidipine might have a beneficial effect on the rheologic behavior of erythrocytes and the improvement of the microcirculation in hypertensive subjects.