Pranidipine, a new 1,4-dihydropyridine (DHP) calcium channel blocker, enhances cyclic GMP-independent nitric oxide (NO)-induced relaxation in the rat aorta

• Published in: Japanese Journal of Pharmacology 1997, Vol.73 (suppl.1), p.43-43
• Main Authors: Toyoki Mori, Tadayoshi Takeuchi, Goro Miyakoda, Makoto Ohura, Hiroyuki Fujiki, Kensuke Orito, Kenji Yoshida, Yoshitaka Yamamura, Fumiaki Hata, Yutaka Nakaya, Hiromu Satake
• Format: Article
• Language: Japanese
• ISSN: 0021-5198

In contrast to amlodipine and nifedipine, pranidipine prolonged endothelium-dependent relaxation induced by acetylcholine (ACh) in rat aorta strips precontracted by prostaglandin F_2α . The phenomenon was inhibited by N-nitro-L-arginine but not modified by presence of indomethacin. Pranidipine had an affinity to DHP receptor but not to other receptors such as muscarinic ACh, histamine H_1 , bradykinin B_2 or vasopressin V_1 . Pranidipine affected neither NO synthase activity nor the time course of a change in vascular cyclic GMP level. Pranidipine did not change Ca^2+ sensitivity to contractile protein or affect cyclic GMP-induced relaxation in the skinned vascular preparations. Pranidipine also prolonged nitroglycerin (NTG)-induced relaxation in the endothelium removed rat aorta, and enhances the relaxation induced by NTG in the presence of methylene blue, a guanylyl cyclase inhibitor. This action was not modified by iberiotoxin, a Ca^2+ -activated K^+ channel inhibitor. These results strongly suggest that pranidipine enhances cyclic GMP-independent NO-induced relaxation, but it is not due to NO-induced hyperpolarization via Ca^2+ -activated K^+ channel activation.