Wiśniewska R J, Wiśniewski K
Department of Pharmacology, Medical Academy of Białystok.
Rocz Akad Med Bialymst. 1998;43:169-85.
The aim of the present study was determinate the role of nitric oxide (NO) in the action of CCK on arterial blood pressure and function of isolated rat heart. Intravenous administration of NO synthase (NOS) inhibitor-NG-nitro-L-arginine methyl ester (L-NAME-100.0 micrograms/kg) increased arterial blood pressure and abolished the hypertensive effect of CCK (administered in the highest dose: 425.0 pmoles/kg i.v.). Donors NO: L-arginine (L-Arg-100.0 mg/kg i.v.) and sodium nitroprusside (SNP-10.0 micrograms/kg i.v.) decreased arterial blood pressure, the hypotensive effect evoked by SNP was greater than produced by L-Arg. CCK administered with L-Arg evoked hypotension (opposite to the hypertensive effect evoked by CCK). When we used CCK at the higher doses (212.5; 425 pmoles/kg i.v.) simultaneously with L-Arg the hypotensive effect was greater than the hypotensive action evoked by L-Arg alone. Administration of CCK with SNP produced the hypotension (similar as after used SNP and opposite to the hypertensive action of the peptide). CCK (21.25, 42.5, 106.25 pmoles/0.1 ml) increased the cardiac contraction amplitude, the peptide injected in lower doses decreased coronary outflow. CCK had no effect on heart rate. L-NAME (10(-5) M) decreased coronary outflow, tendent to evoke bradycardia (p > 0.05) and the compound did not change the cardiac contraction amplitude of isolated heart. L-NAME abolished the influence of CCK on the function of isolated heart. L-Arg (10(-2) M) did not affect function of isolated heart. L-Arg abolished and when we used with CCK in the highest dose reversed the positive inotropic effect of the peptide and tendent to abolish a lowered coronary outflow evoked by CCK. SNP (10(-4) M) decreased the cardiac contraction amplitude. SNP diminished the positive inotropic effect of CCK and did not change other parameters of isolated heart.
NO does not play a role in cardiovascular action of CCK directly, however inhibitor of NO synthase and donors of NO change the influence of the peptide, mainly on the heart. We suggest that the effect is indirectly through catecholamines.
本研究的目的是确定一氧化氮（NO）在胆囊收缩素（CCK）对动脉血压及离体大鼠心脏功能作用中的角色。静脉注射一氧化氮合酶（NOS）抑制剂-NG-硝基-L-精氨酸甲酯（L-NAME-100.0微克/千克）可升高动脉血压，并消除CCK的升压作用（以最高剂量：425.0皮摩尔/千克静脉注射）。一氧化氮供体：L-精氨酸（L-Arg-100.0毫克/千克静脉注射）和硝普钠（SNP-10.0微克/千克静脉注射）可降低动脉血压，SNP引起的降压作用大于L-Arg。与L-Arg一起给予CCK可引起低血压（与CCK引起的升压作用相反）。当我们以较高剂量（212.5；425皮摩尔/千克静脉注射）同时使用CCK和L-Arg时，降压作用大于单独使用L-Arg引起的降压作用。与SNP一起给予CCK可产生低血压（与使用SNP后相似，与该肽的升压作用相反）。CCK（21.25、42.5、106.25皮摩尔/0.1毫升）可增加心脏收缩幅度，以较低剂量注射该肽可减少冠脉流量。CCK对心率无影响。L-NAME（10⁻⁵摩尔/升）可减少冠脉流量，有引起心动过缓的趋势（p>0.05），且该化合物不改变离体心脏的收缩幅度。L-NAME消除了CCK对离体心脏功能的影响。L-Arg（10⁻²摩尔/升）不影响离体心脏功能。L-Arg消除了CCK的正性肌力作用，当与最高剂量的CCK一起使用时可逆转该肽的正性肌力作用，并有消除CCK引起的冠脉流量降低的趋势。SNP（10⁻⁴摩尔/升）可降低心脏收缩幅度。SNP减弱了CCK的正性肌力作用，且不改变离体心脏的其他参数。
NO在CCK的心血管作用中不直接发挥作用，然而一氧化氮合酶抑制剂和一氧化氮供体改变了该肽的影响，主要是对心脏的影响。我们认为这种作用是通过儿茶酚胺间接产生的。
