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 Ca 2+ 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 EC 50 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 Ba 2+ inward current (I Ba ) was examined in A7r5 vascular smooth muscle cells. TPY‐β dose‐dependently inhibited I Ba . The EC 50 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 Ca 2+ 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 Ca 2+ channels can be prevented by TPY‐β‐mediated inhibition of I TO . Drug Dev. Res. 44:87–96, 1998. © 1998 Wiley‐Liss, Inc.