Nifedipine attenuates systemic and renal vasoconstriction during nitric oxide inhibition in humans

被引:29
作者
DijkhorstOei, LT
Rabelink, TJ
Boer, P
Koomans, HA
机构
[1] Dept. of Nephrology and Hypertension, University Hospital Utrecht, 3508 GA Utrecht
关键词
L-NMMA; blood pressure; glomerular filtration rate; calcium channel blockers;
D O I
10.1161/01.HYP.29.5.1192
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
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 N-G-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 Co 29+/-2 mm Hg.min.m(2).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 mu mol/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 mast of these effects, suggesting a role for calcium channel blockade In pathological states of impaired nitric oxide activity.
引用
收藏
页码:1192 / 1198
页数:7
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