环氧化酶和一氧化氮合酶抑制对离体大鼠心脏心脏动力学参数和冠脉血流的影响。

The effects of cyclooxygenase and nitric oxide synthase inhibition on cardiodynamic parameters and coronary flow in isolated rat hearts.

作者信息

Zivkovic Vladimir, Djuric Dragan, Turjacanin-Pantelic Drenka, Marinkovic Zeljko, Stefanovic Djordje, Srejovic Ivan, Jakovljevic Vladimir

机构信息

Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia;

出版信息

Exp Clin Cardiol. 2013 Spring;18(2):e102-10.

PMID:23940446

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3718609/

Abstract

BACKGROUND

Despite the widespread clinical use of cyclooxygenase (COX) inhibitors, dilemmas regarding the potential impact of these drugs on the cardiovascular system persist.

OBJECTIVE

To estimate the effects of different COX inhibitors (meloxicam, acetylsalicylic acid [ASA] and SC-560) on cardiac function and coronary flow in isolated rat hearts, with special focus on the L-arginine/nitric oxide system.

METHODS

The hearts of eight-week-old male Wistar albino rats (n=72; 12 rats per group; body mass 180 g to 200 g) were retrogradely perfused according to the Langendorff technique at gradually increased perfusion pressure (40 cmH2O to 120 cmH2O). After control experiments, the hearts were perfused with the following drugs: 100 μM ASA, alone or in combination with 30 μM N(ω)-nitro-L-arginine monomethyl ester (L-NAME), 0.3 μM meloxicam with or without 30 μM L-NAME, 3 μM meloxicam with or without 30 μM L-NAME, 30 μM L-NAME and 0.25 μM SC-560. In the control and experimental groups, the following parameters of heart function were continuously recorded: maximum rate of left ventricular pressure development, minimum rate of left ventricular pressure development, systolic left ventricular pressure, diastolic left ventricular pressure, heart rate and mean blood pressure. Coronary flow was measured flowmetrically. The amount of released NO2 (-) was determined spectrophotometrically in coronary venous effluent.

RESULTS

While meloxicam and SC-560 were found to have an adverse influence on cardiac function and coronary perfusion, ASA did not negatively affect the intact model of the heart.

CONCLUSION

It appeared that interaction between COX and the L-arginine/nitric oxide system truly exists in coronary circulation and may explain the causes of the observed effects.

摘要

背景

尽管环氧化酶（COX）抑制剂在临床上广泛应用，但这些药物对心血管系统的潜在影响仍存在争议。

目的

评估不同COX抑制剂（美洛昔康、乙酰水杨酸[ASA]和SC-560）对离体大鼠心脏心功能和冠脉血流的影响，特别关注L-精氨酸/一氧化氮系统。

方法

采用Langendorff技术，以逐渐升高的灌注压力（40 cmH₂O至120 cmH₂O）对8周龄雄性Wistar白化大鼠（n = 72；每组12只大鼠；体重180 g至200 g）的心脏进行逆行灌注。在对照实验后，用以下药物灌注心脏：100 μM ASA，单独使用或与30 μM N（ω）-硝基-L-精氨酸甲酯（L-NAME）联合使用；0.3 μM美洛昔康，加或不加30 μM L-NAME；3 μM美洛昔康，加或不加30 μM L-NAME；30 μM L-NAME和0.25 μM SC-560。在对照组和实验组中，连续记录以下心功能参数：左心室压力上升最大速率、左心室压力下降最小速率、左心室收缩压、左心室舒张压、心率和平均血压。用流量测定法测量冠脉血流。用分光光度法测定冠脉静脉流出液中释放的NO₂⁻量。