[Inhibitory effects of palonidipine hydrochloride (TC-81) on contractions induced by various vasoconstrictors in rat aorta].
Inhibitions by palonidipine hydrochloride (TC-81), a new Ca entry blocker, of the contractile responses to norepinephrine (NE), serotonin (5-HT), prostaglandin F2 alpha (PGF2 alpha) and U-46619, a thromboxane A2 analog, were investigated in isolated rat aorta strips and compared with the inhibition of the high K+ response. TC-81 and nicardipine inhibited the contractile responses to NE, 5-HT, PGF2 alpha, and U-46619 in a concentration-dependent manner, but their relative inhibitions were less than 50% at 10(-8) M. In a Ca(2+)-free medium, 2-hr pretreatment with TC-81 or nicardipine did not inhibit the contractile responses to various vasoconstrictors, but it inhibited the responses to the addition of Ca. Their inhibitory potencies were less than the inhibition with high K+. Also, the treatment with TC-81 or nicardipine at 10(-7) M did not affect the tissue level of cyclic AMP. These results suggest that in isolated rat aorta, the inhibition by TC-81 of the contractile responses to NE, 5-HT, PGF2 alpha and U-46619 is not due to inhibition of intracellular Ca2+ release or an increase in cyclic AMP; rather, it is due to inhibition of the Ca2+ influx. This inhibitory effect was less than that seen on the high K+ response.
Pharmaceutical Development Research Laboratories, Teijin Ltd., Tokyo, Japan.
K
K
Aoki
T
T
Kishimoto
K
K
Sunakawa
Y
Y
Okamiya
K
K
Hoshina
T
T
Takeshita
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001011:Aorta / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D015237:Dinoprost / Q000037:antagonists & inhibitors; 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; D011450:Prostaglandin Endoperoxides, Synthetic / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D011450:Prostaglandin Endoperoxides, Synthetic; D012702:Serotonin Antagonists; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C074351:TC 81; D015237:Dinoprost; D002118:Calcium; D009638:Norepinephrine