Kassab S, Miller M T, Hester R, Novak J, Granger J P
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Hypertension. 1998 Jan;31(1 Pt 2):315-20. doi: 10.1161/01.hyp.31.1.315.
Pregnancy-induced hypertension in women is associated with severe vasoconstriction and reductions in organ blood flow and cardiac output. Recent studies have indicated that nitric oxide (NO) synthesis inhibition during mid to late gestation in pregnant rats results in severe hypertension and proteinuria. The purpose of this study was to determine the systemic hemodynamic and regional blood flow alterations associated with chronic NO synthesis inhibition in the pregnant rat. The study was conducted in four groups of rats: virgin rats (n=6), pregnant rats (n=10), virgin rats treated with L-NAME (n=6), and pregnant rats treated with L-NAME (n=11). Rats were treated with L-NAME in drinking water at a dose of 1 mg/d for a week starting from day 13 of gestation in pregnant rats or an equivalent time for virgins. Mean arterial pressure (MAP), cardiac output, total peripheral resistance (TPR), and regional flows were measured by tracing radiolabeled microspheres in conscious rats. Pregnant rats that were given L-NAME showed significantly higher MAP (137+/-6 versus 96+/-2 mm Hg), higher TPR (5.08+/-0.58 versus 2.90+/-0.44 mm Hg/mL/min/100 g), and lower cardiac output (87.4+/-8.4 versus 113.3+/-11.1 mL/min) than pregnant controls. Chronic NO synthesis inhibition decreased the renal blood flow in pregnant rats at a significantly greater magnitude than in virgin rats. Significant reductions in regional blood flow to the heart, lungs, liver, diaphragm, and skeletal muscles were also observed in pregnant rats treated with L-NAME. The results of this study indicate that NO may play a role in mediating the alterations in systemic hemodynamics and regional blood flow in late pregnant rats.
女性妊娠期高血压与严重的血管收缩以及器官血流量和心输出量减少有关。最近的研究表明，妊娠中期至晚期的妊娠大鼠一氧化氮（NO）合成受到抑制会导致严重高血压和蛋白尿。本研究的目的是确定与妊娠大鼠慢性NO合成抑制相关的全身血流动力学和局部血流改变。研究在四组大鼠中进行：未孕大鼠（n = 6）、妊娠大鼠（n = 10）、用L-精氨酸甲酯（L-NAME）处理的未孕大鼠（n = 6）和用L-NAME处理的妊娠大鼠（n = 11）。从妊娠第13天开始，妊娠大鼠或未孕大鼠在相应的等效时间内，以1 mg/d的剂量饮用含L-NAME的水，持续一周。通过在清醒大鼠中追踪放射性标记的微球来测量平均动脉压（MAP）、心输出量、总外周阻力（TPR）和局部血流量。给予L-NAME的妊娠大鼠的MAP（137±6对96±2 mmHg）、TPR（5.08±0.58对2.90±0.44 mmHg/mL/min/100 g）显著更高，心输出量（87.4±8.4对113.3±11.1 mL/min）更低。与未孕大鼠相比，慢性NO合成抑制使妊娠大鼠的肾血流量减少幅度更大。在用L-NAME处理的妊娠大鼠中，还观察到心脏、肺、肝脏、膈肌和骨骼肌的局部血流量显著减少。本研究结果表明，NO可能在介导妊娠晚期大鼠全身血流动力学和局部血流改变中发挥作用。
