肾血流动力学变化及花生四烯酸的P-450代谢产物在单肾单夹高血压逆转中的作用

Role of changes in renal hemodynamics and P-450 metabolites of arachidonic acid in the reversal of one-kidney, one clip hypertension.

作者信息

Zou A P, Muirhead E E, Cowley A W, Mattson D L, Falck J R, Jiang J, Roman R J

机构信息

Department of Physiology, Medical College of Wisconsin, Milwaukee 53226, USA.

出版信息

J Hypertens. 1995 May;13(5):557-66. doi: 10.1097/00004872-199505000-00012.

DOI:10.1097/00004872-199505000-00012

PMID:7561014

Abstract

OBJECTIVE

To examine the role of changes in renal hemodynamics and P-450 metabolites of arachidonic acid in the reversal of one-kidney, one clip (1-K,1C) hypertension in rats.

DESIGN

The stimulus for the release of an antihypertensive lipid from the kidney is not known. This study examined whether cortical or papillary blood flow is altered after removal of the clip from the renal artery of 1-K,1C hypertensive rats, and the effects of blockade of the renal metabolism of arachidonic acid by P-450 with 17-octadecynoic acid (17-ODYA) on the fall in blood pressure.

METHODS

Cortical and medullary blood flows were measured using laser-Doppler flowmetry. 17-ODYA (33 nmol/min) was infused directly into the renal artery to examine the effect of inhibition of renal P-450 activity on reversal of 1-K,1C hypertension. The renal metabolism of arachidonic acid in control and in 1-K,1C hypertensive rats was assessed by incubating microsomes with [14C]-arachidonic acid, the metabolites formed being measured using reverse-phase high-performance liquid chromatography. The antihypertensive effects of these P-450 metabolites of arachidonic acid were compared with those of medullipin I after intravenous administration in conscious spontaneously hypertensive rats (SHR).

RESULTS

Cortical and papillary blood flow increased significantly and arterial pressure fell after unclipping the renal artery in the 1-K,1C hypertensive rats. 17-ODYA prevented the fall in blood pressure after unclipping. The production of epoxy- and dihydroxy-eicosatrienoic acids was elevated in microsomes prepared from the renal cortex of the 1-K,1C hypertensive rats. However, intravenous administration of these metabolites did not mimic the effect of medullipin I to lower arterial pressure in SHR.

CONCLUSION

Elevations in renal cortical or papillary blood flow, or both, may stimulate the release of a P-450-derived antihypertensive lipid from the kidney after unclipping of the renal artery in 1-K,1C hypertensive rats. However, it is unlikely that this substance is a P-450 metabolite of arachidonic acid.

摘要

目的

研究肾血流动力学变化及花生四烯酸的P-450代谢产物在大鼠单肾单夹（1-K，1C）高血压逆转中的作用。

设计

尚不清楚肾脏释放降压脂质的刺激因素。本研究检测了1-K，1C高血压大鼠肾动脉夹去除后皮质或乳头血流是否改变，以及用17-十八碳炔酸（17-ODYA）通过P-450阻断花生四烯酸的肾脏代谢对血压下降的影响。

方法

采用激光多普勒血流仪测量皮质和髓质血流。将17-ODYA（33 nmol/min）直接注入肾动脉，以研究抑制肾P-450活性对1-K，1C高血压逆转的影响。通过用[14C] -花生四烯酸孵育微粒体来评估对照大鼠和1-K，1C高血压大鼠中花生四烯酸的肾脏代谢，使用反相高效液相色谱法测量形成的代谢产物。在清醒的自发性高血压大鼠（SHR）静脉给药后，将这些花生四烯酸的P-450代谢产物的降压作用与髓质素I的降压作用进行比较。