Role of neuropeptide Y in the development of two-kidney, one-clip renovascular hypertension in the rat.
Role of neuropeptide Y in the development of two-kidney, one-clip renovascular hypertension in the rat.
复制标题
神经肽 Y 在大鼠两肾一夹肾血管性高血压发展中的作用。
DOI：
10.1067/mva.2000.108642
复制
发表时间：
2000
影响因子：
4.3
通讯作者：
Beierwaltes,WH
中科院分区：
文献类型：
--
作者：
Shin,LH;Dovgan,PS;Nypaver,TJ;Carretero,OA;Beierwaltes,WH
交感神经刺激可能与肾素-血管紧张素系统一起导致肾血管性高血压。血管活性肽神经肽Y（NPY）通过Y-1受体与去甲肾上腺素共同释放并增强其升压作用。NPY通过增强交感神经活性，可能通过增加肾上腺素能介导的肾素释放，导致肾血管性高血压。通过测定连续Y-1阻断对两肾一夹肾血管性高血压发展的影响以及NPY对体外肾素释放的影响来研究这一点。（10 μg/kg，静脉内给药），以测试在BIBO 3304 TF给药之前和之后的Y-1拮抗剂BIBO 3304 TF。在高血压研究中，28只大鼠接受左肾动脉夹闭。其中，13例植入微型渗透泵，持续输注BIBO 3304 TF（0.3 μg/h，静脉给药）;其他15例接受假植入。然后监测收缩压4周。最后，从肾皮质切片测量体外肾素释放结果BIBO 3304 TF可抑制NPY引起的平均动脉压升高54%（P <0.02）和肾血流量减少38%（P <0.05）。在4周高血压研究中，夹闭对照组的收缩压从130 ± 3 mm Hg增加至167 ± 6 mm Hg（P < .01），而BIBO 3304 TF治疗的大鼠没有显著增加（125 ± 3 mm Hg至141 ± 8 mm Hg）。BIBO 3304 TF治疗组大鼠的最终收缩压比对照组低26 mm Hg（P <0.01）。在肾皮质切片中，没有观察到NPY的影响，在基础或异丙肾上腺素刺激的renin release.ConclusionsThe Y-1受体拮抗剂BIBO 3304 TF衰减急性升压反应，NPY和钝的发展，两肾，一夹肾血管性高血压大鼠。在肾血管性高血压模型中，NPY可能参与高血压反应。我们的体外实验数据并不表明这是由于NPY增强了肾素的释放。（J Vasc Surg 2000;32：1015-21.）
ObjectiveAlong with the renin-angiotensin system, sympathetic stimulation may contribute to renovascular hypertension. The vasoactive peptide neuropeptide Y (NPY) is co-released with and potentiates the pressor effects of norepinephrine through the Y-1 receptor. NPY, by exaggerating sympathetic activity, may contribute to renovascular hypertension, possibly by augmenting adrenergic-mediated renin release. This was studied by determining the effect of continuous Y-1 blockade on the development of two-kidney, one-clip renovascular hypertension and the effect of NPY on in vitro renin release.MethodsMean arterial pressure and renal blood flow responses to NPY (10 μg/kg, administered intravenously) were measured in five anesthetized Sprague-Dawley rats before and after BIBO3304TF administration to test the Y-1 antagonist BIBO3304TF. In hypertension studies, 28 rats underwent left renal artery clipping. Of these, 13 were implanted with a mini-osmotic pump for continuous BIBO3304TF infusion (0.3 μg/h, administered intravenously); the other 15 underwent sham implantation. Systolic blood pressure was then monitored for 4 weeks. Finally, in vitro renin release was measured from renal cortical slices (n = 6-12) incubated with NPY (10–8to 10–6mol/L) or NPY plus the adrenergic agonist isoproterenol (10–4mol/L).ResultsBIBO3304TF attenuated the NPY-induced increase in mean arterial pressure by 54% (P < .02) and the NPY-induced decrease in renal blood flow by 38% (P < .05). In 4-week hypertension studies, systolic blood pressure in clipped controls increased from 130 ± 3 mm Hg to 167 ± 6 mm Hg (P < .01), whereas BIBO3304TF-treated rats had no significant increase (125 ± 3 mm Hg to 141 ± 8 mm Hg). Final systolic blood pressure was 26 mm Hg lower in BIBO3304TF-treated rats than in controls (P < .01). In renal cortical slices, no NPY effect was observed in basal or isoproterenol-stimulated renin release.ConclusionsThe Y-1 receptor antagonist BIBO3304TF attenuated acute pressor responses to NPY and blunted the development of two-kidney, one-clip renovascular hypertension in rats. NPY may contribute to the hypertensive response in this renovascular hypertension model. Our in vitro data do not suggest that this is due to NPY enhancement of renin release. (J Vasc Surg 2000;32:1015-21.)