A possible mechanism on the potentiated vascular effect of coadministration of ifenprodil tartrate and calcium hopantenate: a study in the basilar and vertebral arteries.
In our earlier report [Shibuya et al. in press], we demonstrated the partial mechanism of the synergism between ifenprodil tartrate and calcium hopantenate on cardiovascular diseases. The mechanisms of the synergistic effects in the basilar and vertebral arteries were further studied in this paper using our described methods. Ifenprodil tartrate produced a sustained increase in the vertebral arterial blood flow of rats, while calcium hopantenate. Ifenprodil tartrate caused dose-related relaxation of K+-induced contractions in by ifenprodil tartrate was significantly enhanced by the coadministration of calcium hopantenate. Ifenprodil tartrate caused dose-related relaxation of K+-induced contractions in isolated canine basilar arteries, while calcium hopantenate had no effect. The dose-relaxation curve of ifenprodil tartrate was shifted to the left by pre-incubation in calcium hopantenate. In K+-depolarized basilar arteries, ifenprodil competitively antagonized the response to Ca2+, and this was enhanced by pre-incubation in calcium hopantenate. Ifenprodil tartrate inhibited K+-induced Ca2+ uptake in canine cerebral arteries and this was enhanced by pre-incubation in calcium hopantenate. These results suggest that the enhancement by calcium hopantenate of the ifenprodil tartrate effect on the vertebral blood flow is due to increased vascular relaxation through the inhibition of Ca2+ influx.
Shibuya
T
T
Department of Pharmacology, Tokyo Medical College, Japan.
Honda
H
H
Watanabe
Y
Y
Shimura
H
H
Matsuda
H
H
Tsuji
H
H
Izumisawa
M
M
Iwata
T
T
Irino
O
O
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects*; D001783:Blood Flow Velocity; D002118:Calcium / Q000493:pharmacokinetics*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D008297:Male; D010205:Pantothenic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D010880:Piperidines / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D014711:Vertebral Artery / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology
D010880:Piperidines; C016030:pantogab; D010205:Pantothenic Acid; D005680:gamma-Aminobutyric Acid; C010739:ifenprodil; D002118:Calcium