Alteration of cyclic GMP metabolism by CD-349, a novel calcium antagonist, and by sodium nitroprusside in bovine intrapulmonary artery and vein.
The effects of 2-nitratopropyl 3-nitratopropyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate (CD-349) and sodium nitroprusside (NP) on cyclic GMP (cGMP) metabolism in bovine intrapulmonary artery (BPA) and vein (BPV) were examined. CD-349 inhibited cGMP phosphodiesterase (PDE) activity in BPA and BPV. In the latter, about 40% of the cGMP PDE activity was Ca2+ dependent. The inhibition of cGMP PDE activity by CD-349 also depended on Ca2+. The inhibitory effect of CD-349 was more potent than that of nicardipine or nifedipine. The conversion of cGMP from GTP in the homogenates of BPA and BPV was stimulated by NP in a concentration-dependent manner. The NP-induced cGMP formation was stimulated further by CD-349. This effect of CD-349 depended on Ca2+ in the BPV but not in the BPA. The NP-induced elevation of cGMP levels in the tissue preparations of BPA and BPV was also potentiated by CD-349. These results suggest that CD-349 inhibited Ca2+-dependent cGMP PDE activity and that the levels of cGMP were elevated in vascular smooth muscle, particularly when guanylate cyclase was activated.
Tanaka
M
M
Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Muramatsu
M
M
Aihara
H
H
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002417:Cattle; D006152:Cyclic GMP / Q000378:metabolism*; D004095:Dihydropyridines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005292:Ferricyanides / Q000494:pharmacology*; D066298:In Vitro Techniques; D009599:Nitroprusside / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism*; D011667:Pulmonary Veins / Q000187:drug effects / Q000378:metabolism*
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D005292:Ferricyanides; D009599:Nitroprusside; C054179:CD 349; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006152:Cyclic GMP; D002118:Calcium