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Effects of 1‐pyrrolidinylmethyl‐2‐naphthol on contractile force and ionic current in cardiac and vascular smooth myocytes
Author(s) -
Shen AiYu,
Wu ShengNan
Publication year - 1998
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/(sici)1098-2299(199806/07)44:2/3<87::aid-ddr6>3.0.co;2-6
Subject(s) - contractility , chemistry , myocyte , vasodilation , electrophysiology , vascular smooth muscle , medicine , endocrinology , inhibitory postsynaptic potential , biophysics , cardiac transient outward potassium current , pharmacology , patch clamp , smooth muscle , biology
Abstract 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.