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

✍ Scribed by Ai-Yu Shen; Sheng-Nan Wu

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 191 KB
• Volume: 44
• Category: Article
• ISSN: 0272-4391
• DOI: 10.1002/(sici)1098-2299(199806/07)44:2/3<87::aid-ddr6>3.0.co;2-6

✦ Synopsis

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 .