Mechanisms of inhibitory effects of CD-349 and K(+)-channel activators on noradrenaline-induced contraction and changes in levels of cyclic GMP in rat aorta.
1. CD-349 inhibited the noradrenaline (NA)-induced contraction of aortas in Ca2(+)-free medium. 2. This inhibitory effect was completely antagonized by pretreatment with methylene blue. 3. Nicorandil and cromakalim also inhibited the NA-induced contraction of aortas in Ca2(+)-free medium. 4. The inhibitory effects of nicorandil, but not those of cromakalim, were partially antagonized by pretreatment with methylene blue. 5. The methylene blue-insensitive effects of nicorandil and the effects of cromakalim were antagonized by pretreatment with glibenclamide. 6. These results indicate that the inhibitory effect of CD-349 and nicorandil on NA-induced contraction of aortic strips in Ca2(+)-free medium is mediated through increased levels of cyclic GMP. 7. Furthermore, the inhibitory effect of cromakalim and the partial inhibitory mechanism of nicorandil may be mediated through glibenclamide-sensitive K(+)-channels.
Miyata
N
N
Research Center, Taisho Pharmaceutical Co. Ltd, Saitama, Japan.
Tsuchida
K
K
Kaneko
K
K
Tanaka
M
M
Otomo
S
S
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001578:Benzopyrans / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D019806:Cromakalim; D006152:Cyclic GMP / Q000378:metabolism*; D004095:Dihydropyridines / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D001578:Benzopyrans; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; C054179:CD 349; D006152:Cyclic GMP; D005905:Glyburide; D009638:Norepinephrine