Turkstra E, Braam B, Koomans H A
Department of Nephrology and Hypertension, University Medical Center, Utrecht, The Netherlands.
Hypertension. 2000 Nov;36(5):818-23. doi: 10.1161/01.hyp.36.5.818.
Acute inhibition of angiotensin II formation by angiotensin-converting enzyme inhibition (ACE-I) attenuates tubuloglomerular feedback (TGF) responsiveness. This has been proposed to facilitate sodium excretion, which contributes to the antihypertensive effects of ACE-I. However, in previous experiments in spontaneously hypertensive Fawn-hooded rats, TGF responses were normal during chronic ACE-I treatment. In the present study, we investigated TGF responsiveness during chronic ACE-I treatment in normotensive rats and the involvement of changes in nitric oxide or angiotensin II activity. Maximum TGF responses were assessed in control Sprague-Dawley rats and in rats acutely (acute ACE-I, 3 microgram/min IV) and chronically (chronic ACE-I, 100 mg/L PO 2 to 3 weeks+acute 3 microgram/min enalaprilat IV) treated with ACE-I. In all groups, TGF responses were also assessed during late proximal tubular perfusion with 1 mmol/L nitro-L-arginine. In a last group, the chronic ACE-I treatment was combined with acute ACE-I and high doses of intrarenal losartan (acute 3 microgram/min enalaprilat IV+50 mg/kg losartan). The maximum TGF responses in acutely treated ACE-I rats were strongly attenuated (0.7+/-0.4 mm Hg versus 6.5+/-0.8 mm Hg in control rats, P<0.05). Mean arterial pressure was lower in the chronically treated ACE-I group (107+/-5 mm Hg versus 126+/-5 mm Hg in control rats, P<0.05); however, TGF responses were normal (6. 4+/-0.9 mm Hg). Intraluminal nitro-L-arginine infusion did not influence TGF responses during acute ACE-I (2.3+/-0.4 mm Hg) but enhanced TGF responses during chronic ACE-I to the same extent as in control rats (14.5+/-2.3 versus 16.7+/-1.9 mm Hg, NS). In the rats chronically treated with ACE-I with superimposed acute infusion of losartan or chronically treated with losartan, TGF responses were significantly attenuated (1.8+/-0.8 mm Hg and 2.6+/-0.8 mm Hg, respectively; P:<0.05 versus chronic ACE-I and control). Prolonged administration with ACE-I is associated with normal TGF responses. This phenomenon appears to be mediated by AT1 receptors, because acute treatment with losartan in rats chronically treated with ACE-I and chronic treatment with losartan lead to strong attenuation of TGF responses.
通过抑制血管紧张素转换酶（ACE-I）急性抑制血管紧张素II的形成可减弱肾小管-肾小球反馈（TGF）反应性。这被认为有助于促进钠排泄，从而对ACE-I的降压作用有贡献。然而，在先前对自发性高血压淡黄带帽大鼠的实验中，慢性ACE-I治疗期间TGF反应是正常的。在本研究中，我们调查了正常血压大鼠慢性ACE-I治疗期间的TGF反应性以及一氧化氮或血管紧张素II活性变化的参与情况。在对照的斯普拉格-道利大鼠以及急性（急性ACE-I，静脉注射3微克/分钟）和慢性（慢性ACE-I，口服100毫克/升，持续2至3周+急性静脉注射依那普利拉3微克/分钟）接受ACE-I治疗的大鼠中评估最大TGF反应。在所有组中，在近端肾小管晚期灌注1毫摩尔/升硝基-L-精氨酸期间也评估TGF反应。在最后一组中，慢性ACE-I治疗与急性ACE-I和高剂量肾内氯沙坦联合使用（急性静脉注射依那普利拉3微克/分钟+氯沙坦50毫克/千克）。急性治疗的ACE-I大鼠中的最大TGF反应明显减弱（0.7±0.4毫米汞柱，而对照大鼠为6.5±0.8毫米汞柱，P<0.05）。慢性治疗的ACE-I组的平均动脉压较低（107±5毫米汞柱，而对照大鼠为126±5毫米汞柱，P<0.05）；然而，TGF反应是正常的（6.4±0.9毫米汞柱）。管腔内注入硝基-L-精氨酸在急性ACE-I期间不影响TGF反应（2.3±0.4毫米汞柱），但在慢性ACE-I期间增强TGF反应，其程度与对照大鼠相同（14.5±2.3对16.7±1.9毫米汞柱，无显著性差异）。在慢性接受ACE-I并叠加急性输注氯沙坦或慢性接受氯沙坦治疗的大鼠中，TGF反应明显减弱（分别为1.8±0.8毫米汞柱和2.6±0.8毫米汞柱；与慢性ACE-I和对照相比，P<0.05）。长期给予ACE-I与正常的TGF反应相关。这种现象似乎是由AT1受体介导的，因为在慢性接受ACE-I治疗的大鼠中急性给予氯沙坦以及慢性给予氯沙坦会导致TGF反应强烈减弱。
