Haemodynamic and sympathetic effects of inhibition of nitric oxide synthase by systemic infusion of NG-monomethyl-L-arginine into humans are dose dependent

被引:39
作者
Lepori, M
Sartori, C
Trueb, L
Owlya, R
Nicod, P
Scherrer, U
机构
[1] CHU Vaudois, Dept Internal Med, CH-1011 Lausanne, Switzerland
[2] Univ Lausanne, Inst Physiol, CH-1015 Lausanne, Switzerland
关键词
sympathetic nervous system; nitric oxide; muscle blood flow; inhibition of nitric oxide synthase; infusion of N-G-monomethyl-L-arginine; infusion of phenylephrine; microneurography;
D O I
10.1097/00004872-199816040-00013
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Background In several animal species, nitric oxide (NO) buffers central neural sympathetic outflow, but data concerning humans are sparse and conflicting. We hypothesized that these conflicting results could be related to large differences in the dose of NG. monomethyl-L-arginine, a stereospecific inhibitor of NO synthase, infused in these human studies. Objective To investigate the haemodynamic and sympathetic effects of systemic inhibition of NO synthase by intravenous infusion of two different doses of N-G-menomethyl-L-arginine into healthy humans and compare these effects with those of an equipressor dose of the non-endothelium-dependent vasoconstrictor phenylephrine. Methods Muscle sympathetic nerve activity was measured by microneurography and blood flow by venous occlusion plethysmography, N-G-monomethyl-L-arginine was infused over 15 min at a rate of 50 mu g/kg per min into members of one group (n = 8) and at a rate of 450 mu g/kg per min into members of another group (n = 7), An equipressor dose of phenylephrine was infused into four subjects from each group. Results Infusions of N-G-monomethyl-L-arginine and of phenylephrine at the higher dose similarly suppressed sympathetic activity. In contrast, infusions of NG. monomethyl-L-arginine and of an equipressor dose of phenylephrine at the lower dose had different sympathetic effects. Burst frequency of muscle sympathetic nerve activity remained unchanged during infusion of N-G-monomethyl-L-arginine but decreased by roughly 50% during infusion of phenylephrine, Infusion of N-G-monomethyl-L-arginine at both doses did not alter forearm blood flow, Only infusion of N-G-monomethyl-L-arginine at the higher dose increased forearm vascular resistance. Conclusions Haemodynamic and sympathetic effects of inhibition of NO synthase by infusion of N-G-monomethyl-L-arginine into humans are dose dependent At higher doses, N-G-monomethyl-L-arginine exerts sympathoinhibitory effects that are comparable to those evoked by a non-specific vasoconstrictor drug, whereas at lower doses, it exerts sympatho-excitatory effects. (C) 1998 Lippincott-Raven Publishers.
引用
收藏
页码:519 / 523
页数:5
相关论文
共 26 条
  • [1] MANEUVERS AFFECTING SYMPATHETIC OUTFLOW IN HUMAN MUSCLE NERVES
    DELIUS, W
    HONGELL, A
    WALLIN, BG
    HAGBARTH, KE
    [J]. ACTA PHYSIOLOGICA SCANDINAVICA, 1972, 84 (01): : 82 - &
  • [2] METHODS FOR INVESTIGATION OF PERIPHERAL BLOOD FLOW
    GREENFIELD, ADM
    WHITNEY, RJ
    MOWBRAY, JF
    [J]. BRITISH MEDICAL BULLETIN, 1963, 19 (02) : 101 - &
  • [3] IS NITRIC-OXIDE INVOLVED IN THE TONIC INHIBITION OF CENTRAL SYMPATHETIC OUTFLOW IN HUMANS
    HANSEN, J
    JACOBSEN, TN
    VICTOR, RG
    [J]. HYPERTENSION, 1994, 24 (04) : 439 - 444
  • [4] INHIBITION OF NITRIC-OXIDE FORMATION IN THE NUCLEUS-TRACTUS-SOLITARIUS INCREASES RENAL SYMPATHETIC-NERVE ACTIVITY IN RABBITS
    HARADA, S
    TOKUNAGA, S
    MOMOHARA, M
    MASAKI, H
    TAGAWA, T
    IMAIZUMI, T
    TAKESHITA, A
    [J]. CIRCULATION RESEARCH, 1993, 72 (03) : 511 - 516
  • [5] INHIBITION OF NITRIC-OXIDE SYNTHESIS INCREASES BLOOD-PRESSURE IN HEALTHY HUMANS
    HAYNES, WG
    NOON, JP
    WALKER, BR
    WEBB, DJ
    [J]. JOURNAL OF HYPERTENSION, 1993, 11 (12) : 1375 - 1380
  • [6] MICROINJECTION OF S-NITROSOCYSTEINE INTO THE NUCLEUS-TRACTUS-SOLITARII DECREASES ARTERIAL-PRESSURE AND HEART-RATE VIA ACTIVATION OF SOLUBLE GUANYLATE-CYCLASE
    LEWIS, SJ
    OHTA, H
    MACHADO, B
    BATES, JN
    TALMAN, WT
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 1991, 202 (01) : 135 - 136
  • [7] MONCADA S, 1993, NEW ENGL J MED, V329, P2002
  • [8] Owlya R, 1997, CIRCULATION, V96, P3897
  • [9] Owlya Reza, 1996, Hypertension (Dallas), V28, P512
  • [10] VASCULAR ENDOTHELIAL-CELLS SYNTHESIZE NITRIC-OXIDE FROM L-ARGININE
    PALMER, RMJ
    ASHTON, DS
    MONCADA, S
    [J]. NATURE, 1988, 333 (6174) : 664 - 666