Veratridine augments and BDF 9148 attenuates the spontaneous contractile force of the rat portal vein.
Veratridine and BDF 9148 both increase the force of myocardial contraction but their effects on the contractility of vascular smooth muscle are largely unknown. We have examined the effects of the drugs on the contractile force of the rat portal vein. The force responses of the rat portal vein were not altered by tetrodotoxin (< or = 30 microM) but were augmented by Bay K 8644 (10 nM-10 microM), and attenuated by nifedipine (10 nM-10 micro M). Veratridine slightly reduced the force of spontaneous contractions at concentrations of 0.1-1 microM, then augmented the force at concentrations up to 100 microM. The reduction was prevented by 30 nM tetrodotoxin; a higher concentration of 3 microM prevented the effect of veratridine. Pretreatment with nifedipine at 30 nM reduced the maximum augmentation observed with veratridine. BDF 9148 (0.3-300 microM) attenuated the force and this attenuation was increased in the presence of tetrodotoxin at 3 microM but reversed to an augmentation in the presence of Bay K 8644 at 10 microM. The augmentation produced by BDF 9148 in the presence of Bay K 8644 was reduced by tetrodotoxin at 30 nM. These results suggest that veratridine predominantly opens sodium channels which in turn open voltage-dependent calcium channels to augment the force responses of the rat portal vein, but attenuate force in the presence of sodium-channel blockade with tetrodotoxin. BDF 9148 predominantly closes calcium channels to attenuate the force of the rat portal vein but in the presence of maximum calcium-channel opening with Bay K 8644 augments force probably by opening sodium channels.
Doggrell
S A
SA
Department of Pharmacology, School of Medicine, University of Auckland, New Zealand.
Bishop
B E
BE
D000818:Animals; D001384:Azetidines / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D011169:Portal Vein / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014701:Veratridine / Q000494:pharmacology*
D001384:Azetidines; D002316:Cardiotonic Agents; C071117:BDF 9148; D014701:Veratridine