Verseput G H, Braam B, Provoost A P, Koomans H A
Department of Nephrology, Utrecht University, The Netherlands.
Nephrol Dial Transplant. 1998 Apr;13(4):893-9. doi: 10.1093/ndt/13.4.893.
The spontaneously hypertensive fawn-hooded (FHH) rat develops severe glomerulosclerosis with ageing. The afferent arteriolar resistance is low, resulting in a strongly elevated glomerular capillary pressure (P(GC)).
Afferent arteriolar resistance is under the control of the tubuloglomerular feedback (TGF) system, and we studied whether young FHH rats, i.e. at a stage when only mild glomerulosclerosis was present, have diminished TGF responsiveness.
Maximum TGF-mediated decreases in stop-flow pressure in response to late proximal perfusion with artificial tubular fluid were 9.0 +/- 1.0 mmHg, a value not different or even slightly lower than observed in normal rats. P(GC) was 59.9 +/- 1.2 mmHg and the estimated P(GC) at half-maximal activation of the TGF system (operating P(GC)) was 54.5 +/- 0.8 mmHg at 11 weeks of age (n = 11), a value higher than observed in normal rats. The second question of the present study concerns the effect of chronic angiotensin-I-converting enzyme inhibitor (ACE-i) administration on P(GC). ACE-i, by reducing angiotensin II (Ang II) availability, diminishes TGF responsiveness, which would offset the beneficial effect on P(GC) under normal flow conditions to the macula densa. Maximum TGF responses were 8.9 +/- 1.0 and 17.5 +/- 1.5 mmHg in 11- and 26-week-old rats that had been treated with the ACE-i lisinopril in the drinking water started when the animals were 7 weeks of age. P(GC) was 44.3 +/- 1.2 (n = 9) and operating P(GC) was 40.1 +/- 1.6 mmHg (n = 9) at 11, values significantly lower than in untreated rats. Values remained lower in the 26-week-old treated animals and were 40.9 +/- 0.8 and 32.6 +/- 1.1 mmHg.
(1) the TGF system in this model of spontaneous hypertension and glomerulosclerosis is intact, despite the fact that the FHH rat has a characteristically low afferent arteriolar resistance as compared to other hypertensive rats; (2) the rat displays a normal or even enhanced function of the TGF system following prolonged administration of the ACE-i lisinopril. The latter finding indicates that the reduction of P(GC) achieved by the ACE-i is not offset by a concomitant attenuation of TGF function.
自发性高血压鹿鼠（FHH）随着年龄增长会出现严重的肾小球硬化。入球小动脉阻力较低，导致肾小球毛细血管压力（P(GC)）显著升高。
入球小动脉阻力受肾小管-肾小球反馈（TGF）系统控制，我们研究了年轻的FHH大鼠，即在仅存在轻度肾小球硬化的阶段，其TGF反应性是否降低。
用人工肾小管液晚期近端灌注时，TGF介导的停流压力最大降幅为9.0±1.0 mmHg，该值与正常大鼠中观察到的值无差异，甚至略低。11周龄时（n = 11），P(GC)为59.9±1.2 mmHg，TGF系统半最大激活时的估计P(GC)（工作P(GC)）为54.5±0.8 mmHg，该值高于正常大鼠中观察到的值。本研究的第二个问题涉及长期给予血管紧张素转换酶抑制剂（ACE-i）对P(GC)的影响。ACE-i通过减少血管紧张素II（Ang II）的可用性，降低TGF反应性，这将抵消在正常血流条件下对致密斑的P(GC)的有益作用。在7周龄开始用饮用水中的ACE-i赖诺普利治疗的11周龄和26周龄大鼠中，TGF最大反应分别为8.9±1.0和17.5±1.5 mmHg。11周龄时，P(GC)为44.3±1.2（n = 9），工作P(GC)为40.1±1.6 mmHg（n = 9），这些值显著低于未治疗的大鼠。在26周龄的治疗动物中，这些值仍然较低，分别为40.9±0.8和32.6±1.1 mmHg。
（1）尽管与其他高血压大鼠相比，FHH大鼠具有特征性的低入球小动脉阻力，但在这种自发性高血压和肾小球硬化模型中，TGF系统是完整的；（2）长期给予ACE-i赖诺普利后，大鼠的TGF系统功能正常甚至增强。后一发现表明，ACE-i实现的P(GC)降低不会被TGF功能的同时减弱所抵消。
