Depression of contractions of rabbit aorta and guinea pig vena cava by mesudipine and other slow channel blockers.
The effects of several drugs having Ca++-antagonistic and vasodilating properties were compared in arterial and venous smooth muscles. Developed force (phasic component) was recorded from isolated rings (about 2 mm wide) of blood vessel wall taken from rabbit aorta or guinea pig inferior vena cava. The vascular smooth muscle (VSM) was stimulated to contract for a sustained period by elevating the extracellular K+ concentration ([K]o) to 100 mM or by exposure to norepinephrine (NE). All drugs depressed the K+-induced contractures in a dose-dependent manner between 10(-9) and 10(-5) M. The order of potency in aorta was: mesudipine = verapamil greater than diltiazem greater than nifedipine. Of the three drugs studied in vena cava, the order of potency was: mesudipine greater than verapamil greater than bepridil. It is concluded that, in both preparations of arterial and venous VSM, mesudipine is the most potent inhibitor of K+-induced contractions. Aortic contractions to 10(-7) M NE were depressed at concentrations of Ca++ antagonists 2 or 3 orders of magnitude less than those needed to depress contractions to 10(-5) M NE. The NE-induced contractions were depressed by the drugs to about the same extent as the K+-induced contractions when 10(-7) M NE was used, but were depressed to a much smaller extent when 10(-5) M NE was used. This may reflect the involvement of intracellular Ca++ storage sites in contractions induced by high NE concentrations. It is likely that these drugs depress and block Ca++ influx through the cell membrane.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D015764:Bepridil; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology; D011817:Rabbits; D014682:Vena Cava, Inferior / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D011725:Pyridines; D011759:Pyrrolidines; D015764:Bepridil; D014700:Verapamil; C036653:mesudipine; D004110:Diltiazem; D009543:Nifedipine; D011188:Potassium