Actions of isosorbide dinitrate on smooth muscle cells of rabbit vascular tissues.

ABSTRACT

To investigate the mechanism of the anti-anginal actions of isosorbide dinitrate (ISDN), the effects of this agent on smooth muscle cells of intact and skinned preparations of the rabbit mesenteric artery and vein, and of the coronary artery were studied. ISDN (less than 10(-5) M) had no effect on the membrane potential or resistance of smooth muscle cells of the mesenteric artery and vein under resting conditions, nor when the membrane was depolarized by the presence of various concentrations of [K]o or noradrenaline (NA). The amplitude of spike evoked by outward current pulse after pretreatment with 10 mM tetraethylammonium (TEA) in the mesenteric artery was slightly inhibited by application of 10(-5) M ISDN. The K-induced and NA-induced contractions in the mesenteric artery were not affected by 10(-5) M ISDN, while those evoked in the mesenteric vein were inhibited in concentrations above 10(-6) M. The amplitude and facilitation of excitatory junction potentials evoked by perivascular nerve stimulation in the mesenteric artery were not affected by 10(-5) M ISDN. In skinned muscles, the free calcium concentration (pCa)-tension relationships observed in the mesenteric artery and vein were not affected by 10(-5) M ISDN. This agent had no effect on Ca accumulation into and Ca release from the stores in muscle cells of the mesenteric artery and vein, in skinned preparations. In the rabbit coronary artery, the membrane potential, resistance and spike evoked in the presence of 10 mM TEA were not affected by application of 10(-5) M ISDN. The contraction evoked by excess concentrations of [K]o was not affected. The contraction evoked by a low concentration of acetylcholine (3 X 10(-7) M) but by high concentrations (greater than 10(-6) M) was slightly inhibited by 10(-5) M ISDN. A tonic contraction induced in 39 mM [K]o was reduced by 10(-5) M nitroglycerine but not by 10(-5) M ISDN. Thus in rabbit vascular tissues, ISDN mainly acts on the venous system in vitro. The induced vasodilatation may lead to a reduction in the venous return and hence, reduce oxygen consumption in the cardiac muscles. This effect of ISDN may relate to the anti-anginal actions.