Sandmann S, Yu M, Kaschina E, Blume A, Bouzinova E, Aalkjaer C, Unger T
Institute of Pharmacology, University of Kiel, Germany.
J Am Coll Cardiol. 2001 Jun 15;37(8):2154-65. doi: 10.1016/s0735-1097(01)01287-6.
This study investigated the role of angiotensin receptor subtype 1 (AT1) and angiotensin receptor subtype 2 (AT2) in the regulation of Na+-H+ exchanger (NHE) and Na+-HCO3 symporter (NBC) in the infarcted myocardium.
The cardiac renin-angiotensin system is activated after myocardial infarction (MI), and both angiotensin AT1 and AT2 receptors are upregulated in the myocardium.
Na+-H+ exchanger isoform-1 and NBC-1 gene expression were determined by reverse transcription polymerase chain reaction and Northern blot analysis; protein levels by Western blot analysis; and activity by measurement of H+ transport in left ventricular (LV) free wall, interventricular septum (IS) and right ventricle (RV) after induction of MI. Rats were treated with placebo, the angiotensin-converting enzyme inhibitor ramipril (1 mg/kg/day), the AT1 receptor antagonist valsartan (10 mg/kg/day) or the AT2 receptor antagonist PD 123319 (30 mg/kg/day). Treatment was started seven days before surgery.
Na+-H+ exchanger isoform-1 and NBC-1 messenger RNA (mRNA) expression and protein levels were increased twofold in the LV free wall after MI, whereas no changes were observed in the IS and RV. Na+-dependent H+ flux was increased in the LV free wall. Ramipril inhibited mRNA and protein upregulation of both transporters. Valsartan inhibited the upregulation of NHE-1 mRNA and protein but had no effect on NBC-1 mRNA expression and translation. In contrast, PD 123319 abolished the upregulation of NBC-1 mRNA and protein but had no effect on NHE-1 upregulation. Ramipril and valsartan prevented post-MI increase in NHE-1 activity, whereas ramipril and PD 123319 decreased NBC-1 activity.
Angiotensin II via its AT1 and AT2 receptors differentially controls transcriptional and translational regulation as well as the activity of NHE-1 and NBC-1 in the ischemic myocardium and contributes to the control of pH regulation in cardiac tissue.
本研究调查了1型血管紧张素受体（AT1）和2型血管紧张素受体（AT2）在梗死心肌中对钠氢交换体（NHE）和钠-碳酸氢根协同转运体（NBC）调节中的作用。
心肌梗死后心脏肾素-血管紧张素系统被激活，心肌中血管紧张素AT1和AT2受体均上调。
通过逆转录聚合酶链反应和Northern印迹分析测定钠氢交换体同工型-1和NBC-1基因表达；通过蛋白质印迹分析测定蛋白水平；在诱导心肌梗死后，通过测量左心室游离壁、室间隔和右心室中的氢离子转运来测定活性。大鼠接受安慰剂、血管紧张素转换酶抑制剂雷米普利（1毫克/千克/天）、AT1受体拮抗剂缬沙坦（10毫克/千克/天）或AT2受体拮抗剂PD 123319（30毫克/千克/天）治疗。治疗在手术前7天开始。
心肌梗死后左心室游离壁中钠氢交换体同工型-1和NBC-1信使核糖核酸（mRNA）表达及蛋白水平增加了两倍，而室间隔和右心室中未观察到变化。左心室游离壁中钠依赖性氢离子通量增加。雷米普利抑制了两种转运体的mRNA和蛋白上调。缬沙坦抑制了NHE-1 mRNA和蛋白的上调，但对NBC-1 mRNA表达和翻译无影响。相反，PD 123319消除了NBC-1 mRNA和蛋白的上调，但对NHE-1上调无影响。雷米普利和缬沙坦阻止了心肌梗死后NHE-1活性的增加，而雷米普利和PD 123319降低了NBC-1活性。
血管紧张素II通过其AT1和AT2受体差异地控制转录和翻译调节以及缺血心肌中NHE-1和NBC-1的活性，并有助于心脏组织中pH调节的控制。
