Influence of norepinephrine on the tonic and phasic depression of Vmax by nifedipine and verapamil in guinea pig ventricle.

Right ventricular strips from guinea pig hearts were used to study the interaction between norepinephrine (NE) and the Ca2+ channel blockers nifedipine and verapamil on maximal upstroke velocity (Vmax) of rapid depolarization in potassium-depolarized preparations. Barium ion (0.8 mM) was added to the bathing solution to restore excitability of the K+-depolarized tissue. Concentrations of verapamil (5 X 10(-7) M) and nifedipine (5 X 10(-8) M) were selected to produce optimal depression of Vmax under both tonic (rested) and phasic (pacing frequencies from 0.05 to 2.0 Hz) conditions. NE increased the tonic and phasic Vmax of control preparations in equal proportion at all stimulation frequencies. Thus, the physiological frequency dependence of Vmax was not altered by NE. NE (10(-6) M) produced an increase of 11.8 +/- 2.2% in the tonic Vmax of verapamil-treated preparations and an increase of 17.4 +/- 1.1% in the tonic Vmax of nifedipine-treated preparations. In each case the enhancement of Vmax by NE was proportional for both tonic and phasic conditions, thus showing no effect on the frequency-dependent action of either drug. In all cases, the NE-induced increase in Vmax was concentration dependent. Higher concentrations of NE thwarted the measurement of tonic Vmax due to the onset of spontaneous activity except in the presence of nifedipine (5 X 10(-8) M). The maximal concentration of NE that could be tolerated without the onset of spontaneous activity was directly related to the degree of tonic depression of Vmax induced by the Ca2+ channel blocking agent.(ABSTRACT TRUNCATED AT 250 WORDS)