Fernández-Varo Guillermo, Ros Josefa, Morales-Ruiz Manuel, Cejudo-Martín Pilar, Arroyo Vicente, Solé Manel, Rivera Francisca, Rodés Juan, Jiménez Wladimiro
Hormonal Laboratory, Hospital Clínic Universitari, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona and Instituto Reina Sofia de Investigaciones Nefrológicas, Barcelona, Spain.
Am J Pathol. 2003 Jun;162(6):1985-93. doi: 10.1016/S0002-9440(10)64331-3.
Vascular remodeling is an active process that consists in important modifications in the vessel wall. Endothelium-derived nitric oxide (NO) plays a major role in this phenomenon. We assessed wall thickness (WT), total wall area (TWA), lumen diameter, and total nuclei number/cross-section (TN) in cirrhotic rats with ascites and in control rats. A second group of cirrhotic rats received the NO synthesis inhibitor, L-NAME, or vehicle daily for 11 weeks and systemic hemodynamics, arterial compliance, aortic NO synthase 3 (NOS3) protein expression, and vascular morphology were analyzed. Cirrhotic vessels showed a significant reduction in WT, TWA, and TN as compared to control vessels. Long-term inhibition of NOS activity in cirrhotic rats resulted in a significant increase in WT, TWA, and TN as compared to cirrhotic rats receiving vehicle. NOS3 protein abundance was higher in aortic vessels of nontreated cirrhotic animals than in controls. This difference was abolished by chronic treatment with L-NAME. NOS inhibition in cirrhotic rats resulted in higher arterial pressure and peripheral resistance and lower arterial compliance than cirrhotic rats receiving vehicle. Therefore, vascular remodeling in cirrhosis with ascites is a generalized process with significant functional consequences that can be negatively modulated by long-term inhibition of NOS activity.
血管重塑是一个活跃的过程，包括血管壁的重要改变。内皮衍生的一氧化氮（NO）在这一现象中起主要作用。我们评估了有腹水的肝硬化大鼠和对照大鼠的管壁厚度（WT）、总壁面积（TWA）、管腔直径以及每横截面积的总核数（TN）。第二组肝硬化大鼠每天接受NO合成抑制剂L-NAME或赋形剂，持续11周，然后分析全身血流动力学、动脉顺应性、主动脉一氧化氮合酶3（NOS3）蛋白表达和血管形态。与对照血管相比，肝硬化血管的WT、TWA和TN显著降低。与接受赋形剂的肝硬化大鼠相比，长期抑制肝硬化大鼠的NOS活性导致WT、TWA和TN显著增加。未治疗的肝硬化动物主动脉血管中的NOS3蛋白丰度高于对照组。L-NAME的长期治疗消除了这种差异。与接受赋形剂的肝硬化大鼠相比，抑制肝硬化大鼠的NOS会导致动脉压和外周阻力升高，动脉顺应性降低。因此，伴有腹水的肝硬化中的血管重塑是一个普遍过程，具有显著的功能后果，长期抑制NOS活性可对其产生负面影响。
