Effects of calcium entry blocking agents on 5-hydroxytryptamine- and noradrenaline-induced contractions of rat isolated jugular vein and aorta.
We calculated the contribution of the intracellular releasable calcium pool to the contractile responses induced by 5-hydroxytryptamine (5-HT) and noradrenaline (NA) by constructing time-response curves to the agonists in Ca2+-deficient medium in the isolated rat jugular vein and aorta. Biexponential curves were obtained compatible with a two compartment model. In the aorta the intracellular calcium pools are likely to be different for both 5-HT and NA. Moreover, we investigated the effect of maximally effective concentrations of calcium entry blocking agents (CEB's) on K+, 5-HT- and NA-induced contractions in Ca2+-containing medium. Only a moderate inhibiting effect of nifedipine, diltiazem, flunarizine and gallopamil on 5-HT- and NA-induced Ca2+ influx could be observed; in contrast, K+-induced Ca2+ influx could be antagonized completely. The calculated contribution of intracellular Ca2+ to 5-HT- and NA-induced contractions, obtained from the experiments in Ca2+-"free" medium was much lower than that obtained after pretreatment with CEB's, leading to the conclusion that after CEB-pretreatment a Ca2+ influx component persists. This hypothesis was supported by the observation that contractions in Ca2+-"free" medium consist of a monophasic, fast response only, whereas after CEB-pretreatment a response similar to the control, including a slow, sustained component, was obtained. The Ca2+ influx component not affected by maximally effective concentrations of CEB's seems to represent an inflow of extracellular Ca2+ directly into the cytosol and not into an intracellular calcium store.
Gouw
M A
MA
Division of Pharmacotherapy/Pharmacology, University of Amsterdam, The Netherlands.
Wilffert
B
B
van Zwieten
P A
PA
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004492:Edetic Acid / Q000494:pharmacology; D006207:Half-Life; D066298:In Vitro Techniques; D007601:Jugular Veins / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D012701:Serotonin; D004492:Edetic Acid; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine