Effects of propafenone on 45Ca movements and contractile responses in vascular smooth muscle.
1. In rat isolated aorta the class Ic antiarrhythmic drug, propafenone, dose-dependently inhibited the contractile responses induced by high K (80 mM) and noradrenaline (NA, 10(-5) M), the IC50s being 2.5 +/- 0.7 x 10(-6) M and 8.7 +/- 0.8 x 10(-6) M, respectively. These inhibitory actions were also observed with propafenone added after the induced contractions. 2. Contractile responses induced by addition of Ca to 0 Ca high-K solution were also inhibited by propafenone (IC50 = 2.5 +/- 0.8 x 10(-6) M). Moreover, propafenone inhibited the contractile responses elicited by NA in strips incubated in 0 Ca (IC50 = 1.9 +/- 0.9 x 10(-6) M). 3. Propafenone also inhibited (IC50 = 1.2 +/- 0.4 x 10(-5) M) the development of spontaneous mechanical activity in portal vein segments. 4. Propafenone, 5 x 10(-6) M and 10(-5) M, inhibited 45Ca uptake stimulated by high K or NA without altering 45Ca uptake in resting strips. 5. These results indicated that in rat isolated aortae and portal veins propafenone inhibited Ca entry through voltage-operated channels and NA-induced Ca uptake as well as Ca release from intracellular stores. As a consequence it would reduce the concentration of intracellular free Ca available at the contractile apparatus for vascular smooth muscle contraction.
Carrón
R
R
Department of Pharmacology, School of Medicine, Universidad Complutense, Madrid, Spain.
Pérez-Vizcaino
F
F
Delpón
E
E
Tamargo
J
J
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002132:Calcium Radioisotopes; D005260:Female; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D011405:Propafenone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D002132:Calcium Radioisotopes; D011189:Potassium Chloride; D011405:Propafenone; D002118:Calcium; D009638:Norepinephrine