A COMPARISON OF THE EFFECTS OF VARIOUS SMOOTH MUSCLE RELAXANTS ON THE ELECTRICAL AND MECHANICAL ACTIVITY OF RAT UTERUS

The effects of epinephrine, papaverine, tetracaine and nitroglycerin were studied on the electrical and mechanical activity of isolated segments of myometrium. All four drugs, in concentrations which reduced the force of contractions, decreased the frequency of spontaneous action potential discharge ( i.e. , pacemaker frequency) accompanying each contraction. Tetracaine, papaverine and nitroglycerin also diminished the rising velocity of the individual action potentials, whereas epinephrine increased the rats of rise. The decrease in rising velocity was sometimes accompanied by varying degrees of conduction block. All agents were effective in reducing the contractions elicited by supramaximal electrical field stimulation and the contractures caused by isotonic potassium solutions. Thus, these drugs can exert part of their actions independently of their effects on the electrical activity of the membrane. The inhibitory effects of all four drugs in spontaneously contracting and field-stimulated musclcs were antagonized by increasing the calcium concentration in the bathing medium. In spontaneously contracting muscles, the inhibitory actions of epinephrine and tetracaine on pacemaker frequency and force of contraction and the depressant effect of tetracaine on the rising velocity of the action potentials were also antagonized by the elevated calcium concentration. When the concentration of tetracaine was increased, in the presence of elevated calcium, to a point at which pacemaker frequency was depressed by the drug, the force of contraction was also diminished. However, even at this concentration tetracaine failed to alter the rising velocity of the spikes. It was concluded that, in normally polarized muscles contracting spontaneously, the most important effect of these drugs is a reduction in pacemaker discharge resulting in a decreased action potential frequency, with a subsequent reduction in contractile force. This action may be reinforced in some cases by alteration in cell-to-cell conduction within the muscle.