兔肾动脉和颈总动脉对奥普力农的血管舒张反应差异。

Differential vasodilation response to olprinone in rabbit renal and common carotid arteries.

机构信息

Department of Anesthesiology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-0012, Japan.

出版信息

J Anesth. 2010 Feb;24(1):61-6. doi: 10.1007/s00540-009-0856-y.

DOI:10.1007/s00540-009-0856-y

PMID:20175287

Abstract

PURPOSE

Olprinone, one of the most frequently used phosphodiesterase-3 inhibitors, exerts its positive inotropic and vasodilation effects by inhibiting the degradation of intracellular cyclic adenosine monophosphate (cAMP). The vasodilation response to olprinone is not uniform among the different vascular beds. This study was designed to compare the vasorelaxation response to olprinone between renal and common carotid arteries, and investigate its underlying mechanisms.

METHODS

Isometric force measurement, enzyme immunoassay, and western blotting techniques were used to investigate the vasorelaxation action of olprinone in isolated rabbit renal and common carotid arteries.

RESULTS

Olprinone inhibited the contractile response to phenylephrine (PE) both in the renal and carotid arteries in a concentration-dependent manner with IC50 values of 40 +/- 10 and 103 +/- 43 nM, respectively. The IC50 value was lower (P = 0.004) and the maximal inhibition was greater (P = 0.002) in the renal artery compared with the carotid artery. A cell-permeable cAMP analogue, 8-bromo-cAMP, also inhibited the contractile response to PE in the renal and carotid arteries with IC50 values of 581 +/- 150 and 740 +/- 179 microM, respectively; however no differences were observed both in the IC50 value and the maximal inhibition between two arteries. Olprinone (0.1 microM) increased the intracellular cAMP level in the renal arterial smooth muscle cells (ASMCs) but not in the carotid ASMCs. The expression of PDE3A was greater (P = 0.008) in the carotid ASMCs than the renal ASMCs.

CONCLUSION

The enhanced vasodilator action of olprinone in the renal artery is presumably because of its ability to stimulate the cAMP production, which might be attributable to the heterogeneous expression of PDE3A.

摘要

目的

奥普力农是最常使用的磷酸二酯酶-3 抑制剂之一，通过抑制细胞内环磷酸腺苷（cAMP）的降解来发挥正性肌力和血管扩张作用。奥普力农对不同血管床的血管舒张反应并不一致。本研究旨在比较奥普力农对兔肾动脉和颈总动脉的血管舒张反应，并探讨其潜在机制。

方法

采用等长力测量、酶免疫测定和 Western blot 技术，研究奥普力农对兔离体肾动脉和颈总动脉的血管舒张作用。

结果

奥普力农以浓度依赖性方式抑制肾动脉和颈总动脉对去氧肾上腺素（PE）的收缩反应，IC50 值分别为 40±10 和 103±43 nM。肾动脉的 IC50 值较低（P=0.004），最大抑制作用较大（P=0.002）。一种细胞通透性 cAMP 类似物，8-溴-cAMP，也抑制肾动脉和颈总动脉对 PE 的收缩反应，IC50 值分别为 581±150 和 740±179 microM，但两种动脉之间的 IC50 值和最大抑制作用均无差异。奥普力农（0.1 microM）增加肾动脉平滑肌细胞（ASMCs）中的细胞内 cAMP 水平，但不增加颈总动脉 ASMCs 中的 cAMP 水平。PDE3A 的表达在颈总动脉 ASMCs 中大于肾动脉 ASMCs（P=0.008）。