Effects of 1-pyrrolidinylmethyl-2-naphthol on contractile force and ionic current in cardiac and vascular smooth myocytes

Ionic mechanisms of the cardiovascular actions of 1-pyrrolidinylmethyl- 2-naphthol hydrochloride (TPY-β) were examined. Intravenous infusion of TPY- β produced hypotension and bradycardia in a dose-dependent manner. TPY-β (30 μM) produced biphasic change in contractile force in isolated rat atria, i.e., an initial decrease and a gradual increase. In electrophysiological studies of rat ventricular myocytes, TPY-β dose-dependently suppressed the amplitude of L-type Ca²⁺ inward current (I(Ca,L)), but it did not modify the time constants for I(Ca,L) inactivation and the overall shape of the current-voltage relationship of I(Ca,L). The EC₅₀ value for TPY-β-mediated inhibition of I(Ca,L) is 10.6 ± 1.0 μM. TPY-β (50 μM) mildly suppressed the amplitude of Na⁺ current. TPY-β (50 μM) effectively suppressed the amplitude of transient outward current (I(TO)). The time course for inactivation of I(TO) was changed to a biexponential process after the application of TPY-β. TPY-β (50 μM) also mildly suppressed the amplitude of inwardly rectifying current. In addition, the effect of TPY-β on Ba²⁺ inward current (I(Ba)) was examined in A7r5 vascular smooth muscle cells. TPY-β dose-dependently inhibited I(Ba). The EC₅₀ value for the inhibitory effect of TPY-β is 3.4 ± 0.6 μM. The results indicate that the suppressive effects of TPY-β involve a direct depressant action on heart cells and vascular smooth muscle cells. Thus, direct inhibition of voltage-dependent L- type Ca²⁺ channel is involved in the TPY-β-mediated vasodilatory action. In addition, the inhibitory effect of TPY-β on cardiac contractility through the blockade of L-type Ca²⁺ channels can be prevented by TPY-β-mediated inhibition of I(TO).