Mechanisms Of Vasodilation Of Quateranary Ammonium Salt Derivation(F₃)of Haloperidol

Objectives: Haloperdol (Hal) is an antipsychotic agent, however, our past researches showed that Hal has vessel dilating and cardiac protecting effects. The mechanisms of these effects of F3 ( a quateranary ammonium salt derivation of Hal) were investigated in this study. Methods: 1. All coronary arterial strips in Ca2+-free-Kreb's solution were randomly divided into 7 groups as follows: a. Phen + KCl group b. Phen + KCl +Ver group c. Phen + KCl + F3 group d. Phen + KCl +CaCl2 group e. Phen + KCl +CaCl2 +DMSO group f. Phen + KCl +CaCl2 + Ver groupg. Phen + KCl +CaCl2 + F3 group. And strips in Ca2+-Kreb's solution were divided into 3 groups: a. KCl + Pin + Gli group b. KCl + F3 + Gli group c. KCl + F3 group 2. Effects of F3 on the intracellular Ca2+ level of VSMC: In the laser scanning confocal microscopy (LSCM) experiments, the changes of the intracellular Ca2T fluorescence intensity of VSMC were assessed in the following groups: a. Control group b. KC1+DMSO groupc. KCl + Ver group d. KCl+F3 groupResults'. 1.1 A slight contraction was observed on the coronary arterial strips when 10 μmol/L Phen and 40mmol/LKCl were added into Ca2+-free-Kreb's solution, while the contraction got significantly when 1mmol/L CaCl2 was added in. The contraction was prevented if different concentrations of F3 were added after CaCl2 and the effect showed a dose-effect relationship, when the concentration of f3 was 0.1μmol/L, 1μmol/L 10μmol/L, 100μmol/L was added respectively , the contraction was decreased to 93.44±4.35% (p<0.01), 76.40±8.87%( p <0.01) and 13.35±5.805%, but no changes were found when F3 was added prior to CaCl2. Similar results were found when 0.1μmol/L Ver replaced F3: the contraction was decreased to 67.15±7.57%( p <0.01). 1.2 The contraction was getting strongly when 40mmol/L KCl was added in Ca2+-Kreb's solution, both Pin and different concentrations of F3 inhibited the contraction of the strips, Gli antagonized the effects of Pin but not F3.2. The KCl-induced intracellular Ca2+ fluorescence intensity decreased when F3 or Ver were added. These effects had a dose-effect relationship and a timecourse-effct relationship with the different concentrations ofF3 . The intracellular Ca fluorescence intensity decreased to 73.03± 13.97(p<0.05), 58.16±10.57%( p <0.01), 43.79±16.14%( p<0.01)and 27.51±13.69%( p<0.01) respectively when 2 minutes after F3 at thedifferent concentrations of 0.01μmol/L, 0.1μmol/L, 1μmol/L,10μ mol/L was added respectively. Conclusions:1. Refering to previously experimental results, F3 inhibits the contraction of coronary strips induced by KCl in dose dependently.2. The vessel dilating effect of F3 does not relate to the release ofintracellular Ca2+ , and F3 may not be a ATP sensitive K+ channel opener while it shows an effect of the Ca2+ channel inhibitors.