Protein kinase C-mediated contraction in rabbit aorta is inhibited by CD-349, a dihydropyridine derivative

• Published in: Journal of cardiovascular pharmacology Vol. 17; no. 5; p. 786
• Main Authors: Miyata, N, Tsuchida, K, Otomo, S
• Format: Journal Article
• Language: English
• Published: United States 01.05.1991
• Subjects: Animals; Aorta, Thoracic - drug effects; Atrial Natriuretic Factor - pharmacology; Calcium Channel Blockers - pharmacology; Cyclic AMP - physiology; Dihydropyridines - pharmacology; Endothelins - pharmacology; Male; Muscle Contraction - drug effects; Nitroglycerin - pharmacology; Phorbol 12,13-Dibutyrate - pharmacology; Protein Kinase C - physiology; Rabbits
• ISSN: 0160-2446
• DOI: 10.1097/00005344-199105000-00014

We investigated the effects of nitroglycerin (NTG), atrial natriuretic peptide (ANP), and CD-349 on phorbol dibutyrate (PDBu)-induced contraction in rabbit aorta. In the presence of endothelium, both NTG (10(-8)-10(-5) M) and ANP (10(-10)-10(-7) M) inhibited the PDBu-induced contraction in a concentration-dependent manner. CD-349 (10(-8)-10(-5) M) also inhibited the PDBu-induced contraction in a concentration-dependent manner. This inhibitory effect of CD-349 was independent of the existence of endothelium. Inhibitory effects of both NTG and CD-349 but not ANP were antagonized by treatment with methylene blue. However, nifedipine (10(-5) M), nicardipine (10(-5) M), and diltiazem (10(-5) M) had little or no effect on PDBu-induced contraction. Furthermore, NTG, ANP, and CD-349 inhibited endothelin-induced contraction, which may be mediated through activation of protein kinase C. These results indicate that PDBu-induced and endothelin-induced contractions in rabbit aorta are inhibited by agents known to elevate vascular cyclic GMP content.