Nava E, Farré A L, Moreno C, Casado S, Moreau P, Cosentino F, Lüscher T F
Department of Cardiology, University Hospital, Zürich, Switzerland.
J Hypertens. 1998 May;16(5):609-15. doi: 10.1097/00004872-199816050-00008.
To examine the role of nitric oxide in the cardiovascular system in spontaneous hypertension. In particular, we wanted to know whether the production of nitric oxide in the cardiovascular system of the spontaneously hypertensive rat is different from that of the normotensive Wistar-Kyoto rat and whether nitric oxide is biologically effective in this system.
We studied various aspects of the L-arginine-nitric oxide pathway in the cardiovascular system of spontaneously hypertensive rats and Wistar-Kyoto rats.
To address the first objective we analysed the expression of endothelial nitric oxide synthase in the heart by Western blotting and the activity of constitutive nitric oxide synthase in resistance microvessels obtained from the mesenterium, both from spontaneously hypertensive rats and Wistar-Kyoto rats aged 14-18 weeks. We also analysed the concentration of the oxidative product of nitric oxide, nitrate, in plasma from these rats. To address the second objective, that is, to assess the bioactivity of nitric oxide, we studied the accumulation in tissue of cyclic guanosine 3',5'-monophosphate (GMP), as well as the acute and chronic effects of withdrawing the nitric oxide vasodilatory tone with the inhibitor of nitric oxide synthesis NG-nitro-L-arginine methyl ester on Wistar-Kyoto rats and spontaneously hypertensive rats.
We found that the expression of endothelial nitric oxide synthase in the heart, the activity of constitutive nitric oxide synthase in resistance microvessels and the concentration of nitrate in plasma were all significantly higher in the spontaneously hypertensive rats. In contrast, neither cyclic GMP levels nor the effects of NG-nitro-L-arginine methyl ester were greater in the spontaneously hypertensive rat than they were in the Wistar-Kyoto rat.
The nitric oxide pathway is upregulated in the resistance circulation and the heart of the spontaneously hypertensive rat by a mechanism involving induction of the constitutive nitric oxide synthase and overproduction of nitric oxide. However, nitric oxide is not sufficiently bioactive to stimulate the formation of cyclic GMP and to maintain an adequate nitric oxide-dependent vasodilatory tone.
研究一氧化氮在自发性高血压心血管系统中的作用。具体而言，我们想了解自发性高血压大鼠心血管系统中一氧化氮的产生是否与正常血压的Wistar-Kyoto大鼠不同，以及一氧化氮在该系统中是否具有生物学效应。
我们研究了自发性高血压大鼠和Wistar-Kyoto大鼠心血管系统中L-精氨酸-一氧化氮途径的各个方面。
为实现第一个目标，我们通过蛋白质印迹法分析了14-18周龄自发性高血压大鼠和Wistar-Kyoto大鼠心脏中内皮型一氧化氮合酶的表达，以及从肠系膜获取的阻力微血管中组成型一氧化氮合酶的活性。我们还分析了这些大鼠血浆中一氧化氮的氧化产物硝酸盐的浓度。为实现第二个目标，即评估一氧化氮的生物活性，我们研究了环磷酸鸟苷（cGMP）在组织中的积累，以及用一氧化氮合成抑制剂NG-硝基-L-精氨酸甲酯消除一氧化氮血管舒张张力对Wistar-Kyoto大鼠和自发性高血压大鼠的急性和慢性影响。
我们发现，自发性高血压大鼠心脏中内皮型一氧化氮合酶的表达、阻力微血管中组成型一氧化氮合酶的活性以及血浆中硝酸盐的浓度均显著高于Wistar-Kyoto大鼠。相比之下，自发性高血压大鼠的cGMP水平和NG-硝基-L-精氨酸甲酯的作用均不比Wistar-Kyoto大鼠更强。
自发性高血压大鼠的阻力循环和心脏中一氧化氮途径通过一种涉及组成型一氧化氮合酶诱导和一氧化氮过量产生的机制上调。然而，一氧化氮的生物活性不足以刺激cGMP的形成并维持足够的一氧化氮依赖性血管舒张张力。
