Tschudi M R, Noll G, Arnet U, Novosel D, Ganten D, Lüscher T F
Department of Research, University Hospital Basel, Switzerland.
Circulation. 1994 Jun;89(6):2780-6. doi: 10.1161/01.cir.89.6.2780.
The renin-angiotensin system and endothelium-derived nitric oxide (EDNO) are important regulators of vascular tone. This study was designed to investigate endothelial and vascular smooth muscle function in coronary arteries of Ren-2 transgenic rats.
Left anterior descending coronary arteries and aortas were isolated from transgenic rats and Sprague-Dawley control rats at 6 (young) and 12 (adult) weeks of age and examined in myographs or organ chambers for isometric tension recording. Systolic blood pressure was significantly higher in transgenic rats (young, 229 +/- 6 mm Hg; adult, 239 +/- 8 mm Hg) than in control rats (young, 126 +/- 2 mm Hg; adult, 118 +/- 3 mm Hg; P < .005). N omega-Nitro-L-arginine methyl ester (L-NAME, 10(-7) to 10(-4) mol/L) evoked marked endothelium-dependent contractions in coronary arteries (young, 52 +/- 8% of the contraction to 100 mmol/L KCl; adult, 40 +/- 8%) but not aortas (young, 3 +/- 1%; adult, 2 +/- 1%). In coronary arteries, this response was significantly smaller in adult (n = 9) than in young (n = 8, P < .05) control rats. Young transgenic rats (56 +/- 9%, n = 8) showed slightly stronger contractions in response to L-NAME than young control rats (NS), which almost totally disappeared in adult transgenic rats (6 +/- 3%, n = 7; P < .05 versus adult control rats; P < .01 versus young transgenic rats). Endothelium-dependent relaxations in response to acetylcholine (10(-9) to 10(-4) mol/L) were totally blocked by L-NAME (10(-4) mol/L) but were unaffected by the thromboxane receptor antagonist SQ30741 (10(-7) mol/L). This stimulated release of EDNO, endothelium-independent relaxations in response to the nitrovasodilator linsidomine (10(-9) to 10(-5) mol/L), and contractions in response to KCl (100 mmol/L) were comparable in all groups of rats.
Ren-2 transgenic rats develop fulminant hypertension that is associated with a selective decrease in endothelium-dependent contractions in response to L-NAME, whereas endothelium-dependent relaxations in response to acetylcholine as well as smooth muscle function remain unaffected.
肾素 - 血管紧张素系统和内皮衍生的一氧化氮（EDNO）是血管张力的重要调节因子。本研究旨在调查Ren - 2转基因大鼠冠状动脉的内皮和血管平滑肌功能。
在6周龄（幼年）和12周龄（成年）时，从转基因大鼠和Sprague - Dawley对照大鼠中分离出左前降支冠状动脉和主动脉，并在肌动描记器或器官浴槽中进行等长张力记录。转基因大鼠的收缩压（幼年，229±6 mmHg；成年，239±8 mmHg）显著高于对照大鼠（幼年，126±2 mmHg；成年，118±3 mmHg；P <.005）。Nω - 硝基 - L - 精氨酸甲酯（L - NAME，10⁻⁷至10⁻⁴mol/L）在冠状动脉中引起明显的内皮依赖性收缩（幼年，为对100 mmol/L氯化钾收缩的52±8%；成年，40±8%），但在主动脉中未引起（幼年，3±1%；成年，2±1%）。在冠状动脉中，成年（n = 9）对照大鼠的这种反应明显小于幼年（n = 8，P <.05）对照大鼠。幼年转基因大鼠（56±9%，n = 8）对L - NAME的收缩反应略强于幼年对照大鼠（无显著性差异），而在成年转基因大鼠中几乎完全消失（6±3%，n = 7；与成年对照大鼠相比，P <.05；与幼年转基因大鼠相比，P <.01）。对乙酰胆碱（10⁻⁹至10⁻⁴mol/L）的内皮依赖性舒张被L - NAME（10⁻⁴mol/L）完全阻断，但不受血栓素受体拮抗剂SQ30741（10⁻⁷mol/L）影响。所有大鼠组中，这种刺激释放的EDNO、对硝基血管扩张剂林西多明（10⁻⁹至10⁻⁵mol/L）的非内皮依赖性舒张以及对氯化钾（100 mmol/L）的收缩反应相当。
Ren - 2转基因大鼠发生暴发性高血压，这与对L - NAME的内皮依赖性收缩选择性降低有关，而对乙酰胆碱的内皮依赖性舒张以及平滑肌功能保持未受影响。
