Protein kinase C-mediated contraction in rabbit aorta is inhibited by CD-349, a dihydropyridine derivative.
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.
Miyata
N
N
Research Center, Taisho Pharmaceutical, Saitama, Japan.
Tsuchida
K
K
Otomo
S
S
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D000242:Cyclic AMP / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology*; D016232:Endothelins / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D005996:Nitroglycerin / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology*; D011817:Rabbits
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D016232:Endothelins; D015240:Phorbol 12,13-Dibutyrate; D009320:Atrial Natriuretic Factor; C054179:CD 349; D000242:Cyclic AMP; D011493:Protein Kinase C; D005996:Nitroglycerin