使用反向微透析技术对主动脉缩窄大鼠下丘脑血管紧张素系统的研究。

Study of the hypothalamic angiotensin system in aortic coarctated rats using the reverse microdialysis technique.

作者信息

Höcht Christian, Opezzo Javier A W, Gironacci Mariela, Peña Clara, Taira Carlos A

机构信息

Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Junín 956, (C1113AAD) Buenos Aires, Argentina.

出版信息

Pharmacol Res. 2003 Sep;48(3):301-7. doi: 10.1016/s1043-6618(03)00126-9.

DOI:10.1016/s1043-6618(03)00126-9

PMID:12860451

Abstract

The objective of our work was to study the intrahypothalamic actions of irbesartan, an angiotensin receptor antagonist, on blood pressure and dopaminergic and serotoninergic neurotransmission in sham operated (SO) and aortic coarctated (ACo) rats by using the microdialysis perfusion technique. We also studied a possible enhanced pressor response to angiotensin II in aortic coarctated rats in the anterior and posterior hypothalamic area. Wistar urethane-chloralose anaesthetised rats were used. A cannula was inserted in the carotid artery. A concentric microdialysis probe was implanted into the anterior hypothalamus or posterior hypothalamus and irbesartan (6 microg ml(-1)) was perfused through the probe. Changes of mean arterial pressure (MAP) were measured. 3,4-Dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) levels were measured in dialysate samples by HPLC-EC. A greater response to irbesartan perfusion in the anterior hypothalamic area of aortic coarctated rats was observed (SO rats, DMAP: -4.3+/-2.3 mm Hg; ACo rats, DMAP: -11.4+/-1.5 mm Hg, P<0.05). The pressor response to angiotensin II in the anterior hypothalamic area (SO rats, DMAP: 4.2+/-1.2 mm Hg; ACo rats, DMAP: 21.7+/-3.7 mm Hg, P<0.05) but not in the posterior hypothalamic area was enhanced in aortic coarctated rats. The perfusion of irbesartan in the anterior hypothalamic area did not modify the extracellular levels of 5-HIAA in both experimental groups, but induced a slightly reduction of DOPAC levels in sham operated rats. The results suggest that the angiotensin system in the anterior hypothalamic area is involved in the maintenance of hypertension in ACo rats and it appears that the increased pressor reactivity to angiotensin II is related to this enhanced function. On the other hand, the effect of irbesartan on DOPAC dialysate levels suggests that the drug produces an alteration of the dopaminergic neurotransmission in the SO rats.

摘要

我们研究的目的是通过微透析灌注技术，研究血管紧张素受体拮抗剂厄贝沙坦对假手术（SO）和主动脉缩窄（ACo）大鼠下丘脑内血压以及多巴胺能和5-羟色胺能神经传递的作用。我们还研究了主动脉缩窄大鼠下丘脑前部和后部区域对血管紧张素II升压反应可能增强的情况。使用Wistar乌拉坦-氯醛糖麻醉的大鼠。在颈动脉插入一根套管。将同心微透析探针植入下丘脑前部或后部，并通过探针灌注厄贝沙坦（6微克/毫升）。测量平均动脉压（MAP）的变化。通过高效液相色谱-电化学检测法测量透析液样本中3,4-二羟基苯乙酸（DOPAC）和5-羟吲哚乙酸（5-HIAA）的水平。观察到主动脉缩窄大鼠下丘脑前部区域对厄贝沙坦灌注的反应更大（SO大鼠，MAP变化：-4.3±2.3毫米汞柱；ACo大鼠，MAP变化：-11.4±1.5毫米汞柱，P<0.05）。主动脉缩窄大鼠下丘脑前部区域对血管紧张素II的升压反应增强（SO大鼠，MAP变化：4.2±1.2毫米汞柱；ACo大鼠，MAP变化：21.7±3.7毫米汞柱，P<0.05），而下丘脑后部区域则未增强。在两个实验组中，下丘脑前部区域灌注厄贝沙坦均未改变5-HIAA的细胞外水平，但在假手术大鼠中导致DOPAC水平略有降低。结果表明，下丘脑前部区域的血管紧张素系统参与了ACo大鼠高血压的维持，并且对血管紧张素II升压反应性的增加似乎与这种功能增强有关。另一方面，厄贝沙坦对DOPAC透析液水平的影响表明，该药物在SO大鼠中引起了多巴胺能神经传递的改变。