Dijkhorst-Oei L T, Rabelink T J, Boer P, Koomans H A
Department of Nephrology and Hypertension, University Hospital Utrecht, Netherlands.
Hypertension. 1997 May;29(5):1192-8. doi: 10.1161/01.hyp.29.5.1192.
Clinical states associated with nitric oxide deficiency are often accompanied by vasoconstriction. We studied the effects of prolonged infusion of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) on systemic and renal hemodynamics in humans and the reversibility of the established vasoconstriction by calcium channel blockade with nifedipine. Seven healthy men underwent three 7-hour clearance studies. During one study, L-NMMA (3 mg/kg priming dose plus 3 mg.kg-1.h-1) was infused during hours 2 through 5, and during another study, nifedipine (0.015 mg/kg priming dose plus 0.015 mg.kg-1.h-1) was coinfused during hours 4 and 5. A third study served as time control. L-NMMA elicited reproducible systemic and renal vasoconstriction that was stable during the 4 hours of infusion. Systemic vascular resistance index, calculated from bioimpedance-derived cardiac index, increased from 22 +/- 1 to 29 +/- 2 mm Hg.min.m2.L-1 (P < .05). Mean arterial pressure rose by 4 +/- 1 mm Hg (P < .05), and heart rate, stroke index, and cardiac index decreased. Renal blood flow, calculated from renal plasma flow, decreased from 1182 +/- 101 to 785 +/- 53 mL/min, and renal vascular resistance increased from 73 +/- 5 to 115 +/- 6 mm Hg.min.L-1 (P < .05). Glomerular filtration rate decreased from 114 +/- 6 to 104 +/- 6 mL/min (P < .05), and filtration fraction increased. Sodium excretion fell from 89 +/- 9 to 32 +/- 7 mumol/min (P < .05). Nifedipine completely reversed systemic vasoconstriction. Nifedipine caused partial restoration of renal vascular resistance and complete normalization of glomerular filtration rate and sodium excretion but left the elevated filtration fraction unaltered. We conclude that sustained nitric oxide deficiency in humans is accompanied by strong systemic and renal vasoconstriction, decreased glomerular filtration rate, and sodium retention. Nifedipine can reverse most of these effects, suggesting a role for calcium channel blockade in pathological states of impaired nitric oxide activity.
与一氧化氮缺乏相关的临床状态常伴有血管收缩。我们研究了长时间输注一氧化氮合酶抑制剂NG-单甲基-L-精氨酸（L-NMMA）对人体全身和肾脏血流动力学的影响，以及硝苯地平钙通道阻滞对已建立的血管收缩的可逆性。七名健康男性进行了三项7小时的清除率研究。在一项研究中，在第2至5小时输注L-NMMA（3mg/kg负荷剂量加3mg·kg⁻¹·h⁻¹），在另一项研究中，在第4和5小时同时输注硝苯地平（0.015mg/kg负荷剂量加0.015mg·kg⁻¹·h⁻¹）。第三项研究作为时间对照。L-NMMA引起可重复的全身和肾脏血管收缩，在输注的4小时内保持稳定。根据生物阻抗衍生的心脏指数计算的全身血管阻力指数从22±1增加到29±2mmHg·min·m²·L⁻¹（P<.05）。平均动脉压升高4±1mmHg（P<.05），心率、每搏指数和心脏指数降低。根据肾血浆流量计算的肾血流量从1182±101降至785±53mL/min，肾血管阻力从73±5增加到115±6mmHg·min·L⁻¹（P<.05）。肾小球滤过率从114±6降至104±6mL/min（P<.05），滤过分数增加。钠排泄从89±9降至32±7μmol/min（P<.05）。硝苯地平完全逆转了全身血管收缩。硝苯地平使肾血管阻力部分恢复，肾小球滤过率和钠排泄完全恢复正常，但升高的滤过分数未改变。我们得出结论，人体持续的一氧化氮缺乏伴有强烈的全身和肾脏血管收缩、肾小球滤过率降低和钠潴留。硝苯地平可以逆转这些影响中的大部分，提示钙通道阻滞在一氧化氮活性受损的病理状态中起作用。
