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Pranidipine, a new 1, 4-dihydropyridine calcium channel blocker, enhances cyclic GMP-independent nitric oxide-induced relaxation of the rat aorta

Authors
  • Mori, Toyoki1
  • Takeuchi, Tadayoshi2
  • Ohura, Makoto1
  • Miyakoda, Goro1
  • Fujiki, Hiroyuki1
  • Orito, Kensuke1
  • Yoshida, Kenji1
  • Hirano, Takahiro1
  • Yamamura, Yoshitaka1
  • Sumida, Takumi1
  • Nakaya, Yutaka3
  • Satake, Hiromu4
  • Hata, Fumiaki2
  • 1 Otsuka Pharmaceutical Co. Ltd., 2nd Tokushima Institute of New Drug Research, 463-10 Kagasuno, Kawauchi-cho, Tokushima, 771-01, Japan , Kawauchi-cho, Tokushima
  • 2 University of Osaka Prefecture, Department of Veterinary Pharmacology, 1-1 Gakuen-machi, Sakai, Osaka, 593, 4Japan , Sakai, Osaka
  • 3 Tokushima University School of Medicine, Department of Nutrition, 2-50-1 Kuramoto, Tokushima, 770, Japan , Tokushima
  • 4 Tokushima University, Center for Coordination, 1 Minamijousanjima, Tokushima, 770, Japan
Type
Published Article
Journal
Molecular and Cellular Biochemistry
Publisher
Springer-Verlag
Publication Date
Jan 01, 1998
Volume
178
Issue
1-2
Pages
335–343
Identifiers
DOI: 10.1023/A:1006827801386
Source
Springer Nature
Keywords
License
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Abstract

Pranidipine, a new calcium channel modulator, prolonged endothelium-dependent relaxation induced by acetylcholine in a aortic ring preparation, contracted with prostaglandin F2α. This action was not shared by amlodipine. The effect was not modified by indomethacin, suggesting that the action of pranidipine does not involve prostanoid metabolism. NG-nitro-L-arginine completely prevented the action of Pranidipine. The drug affected neither nitric oxide (NO) synthase activity nor the level of cyclic GMP in the vessel. Pranidipine did not affect the sensitivity of the contractile proteins to calcium. Pranidipine also did not alter cyclic GMP-induced relaxation in a-toxinskinned vascular preparations. Pranidipine also prolonged glyceryl trinitrate-induced relaxation in the endothelium denuded rat aorta. Furthermore, pranidipine enhanced relaxation of the aorta induced by glyceryl trinitrate even in the presence of methylene blue, a guanylyl cyclase inhibitor. This action was not modified by iberiotoxin or by charybdotoxin, two inhibitors of the calciumactivated potassium channel. The results strongly suggest that pranidipine enhances cyclic GMPindependent NO-induced relaxation of smooth muscle by a mechanism other than through NOinduced hyperpolarization. These effects were in direct contrast to amlodipine, another new 1,4dihydropyridine calcium antagonist.

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