Altered NGF regulation may link a genetic predisposition for hypertension with hyperactive voiding
Altered NGF regulation may link a genetic predisposition for hypertension with hyperactive voiding
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DOI：
10.1016/s0022-5347(01)61686-0
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发表时间：
1999-04-01
影响因子：
6.6
通讯作者：
Tuttle, JB
中科院分区：
文献类型：
--
作者：
Clemow, DB;Spitsbergen, JM;Tuttle, JB
目的：自发性高血压大鼠(SHR)的特点是排尿过度活跃，血管内神经生长因子(NGF)产量增加。靶来源的NGF升高与SHR的高血压和排尿过度活跃有关。在本研究中，我们检测了高血压、排尿多动和膀胱平滑肌细胞(BSMC)NGF分泌增加之间可能的遗传联系。材料和方法：我们将SHR与WKYS杂交，产生一个基因分离的F2群体。测量F2平均动脉压(BP)和6小时排尿频率。从低血压F2s(95+/-2)和高BPF2s(141+/-3 mm)培养BSMCs。Hg)和条件培养液进行NGF双点酶联免疫吸附试验。结果：F2代BSMC的血压与排尿率呈正相关(r=0.75)。随着血压升高，排尿频率增加，单位尿量减少，排尿总量无明显变化(低血压F2s：1.0+/-0.5；高血压F2s：6.2+/-0.5/6h)。低血压F2s(2.0+/-0.2)分泌NGF的基础速率高于高BPF2s(0.7+/-0.1fg NGF/hr/100细胞)。然而，高BP F2组(1,620和3,850)对异丙肾上腺素和PDGF诱导的NGF产量增加过度敏感，而低BP F2组(分别为219和1,282%对照)对NGF产量的增加过于敏感。结论：组织NGF的升高是由于对NGF调节刺激的高敏感性，而不是基础NGF的变化，可能与高血压和排尿过度有关。
Purpose: Hyperactive voiding and elevated smooth muscle NGF output are traits of the spontaneously hypertensive rat (SHR). Elevated target-derived NGF is associated with hypertension and hyperactive voiding in SHRs. In the present study, we tested for possible genetic links between hypertension, hyperactive voiding and augmented bladder smooth muscle cell (BSMC) NGF secretion.Materials and Methods: We crossed SHRs with WKYs to produce a gene segregating F2 population. We measured F2 mean arterial blood pressure (BP) and six-hour voiding frequency. BSMCs were cultured from 'Low BP F2s' (95 +/- 2) and 'High BP F2s' (141 +/- 3 mm. Hg) and conditioned medium tested for NGF with a two-site ELISA. The NGF regulators isoproterenol, platelet-derived growth factor (PDGF) and phorbol-12-myristate-13-acetate were tested in F2 BSMC cultures.Results: A positive correlation (r = 0.75) between blood pressure and voiding frequency existed in this F2 population. As BP rose voiding frequency increased and volume per void decreased such that there were no significant changes in total urine voided (Low BP F2s: 1.0 +/- 0.5; High BP F2s: 6.2 +/- 0.5 voids/6 hours). Low BP F2s (2.0 +/- 0.2) secreted NGF at a higher basal rate than High BP F2s (0.7 +/- 0.1 fg NGF/hr/100 cells). However, High BP F2s (1,620 and 3,850) were oversensitive to isoproterenol and PDGF-induced increases in NGF output, compared with Low BP F2s (219 and 1,282% control, respectively).Conclusions: Elevated tissue NGF due to a hypersensitivity to NGF regulating stimuli, rather than alterations in basal NGF, may genetically link hypertension and hyperactive voiding.