ADMA increases arterial stiffness and decreases cerebral blood flow in humans

被引:210
作者
Kielstein, Jan T. [1 ]
Donnerstag, Frank
Gasper, Sandra
Menne, Jan
Kielstein, Anousheh
Martens-Lobenhoffer, Jens
Scalera, Fortunato
Cooke, John P.
Fliser, Danilo
Bode-Boeger, Stefanie M.
机构
[1] Stanford Univ, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA
[2] Hannover Med Sch, Dept Nephrol, D-3000 Hannover, Germany
[3] Hannover Med Sch, Dept Neuroradiol, D-3000 Hannover, Germany
[4] Hannover Med Sch, Dept Psychiat, D-3000 Hannover, Germany
[5] Otto Von Guericke Univ, Inst Clin Pharmacol, Magdeburg, Germany
关键词
cerebral blood flow; hemodynamics; nitric oxide; stroke; ischemic; vascular resistance;
D O I
10.1161/01.STR.0000231640.32543.11
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background and Purpose-Preclinical studies have revealed that the endogenous nitric oxide synthase inhibitor, asymmetric dimethylarginine (ADMA), increases vascular tone in cerebral blood vessels. Marked elevations of ADMA blood levels were found in patients with diseases characterized by decreased cerebral perfusion, such as ischemic stroke. Arterial stiffness is an independent predictor of stroke and other adverse cardiovascular events. The aim of this study was to investigate the influence of a systemic subpressor dose of ADMA on arterial stiffness and cerebral perfusion in humans. Methods-Using a double-blind, vehicle-controlled study design, we allocated 20 healthy men in random order to infusion of either ADMA (0.10 mg ADMA/kg per min) or vehicle over a period of 40 minutes. Arterial stiffness was assessed noninvasively by pulse wave analysis. All volunteers underwent measurement of cerebral perfusion by dynamic contrast-enhanced perfusion magnetic resonance imaging of the brain. Results-Infusion of ADMA significantly decreased total cerebral perfusion by 15.1 +/- 4.5% (P=0.007), whereas blood flow in the vehicle group increased by 7.7 +/- 2.8% (P=0.02). ADMA also increased arterial stiffness as assessed by measurement of the augmentation index (-12.6 +/- 1.9 to -9.6 +/- 1.5, P=0.007). Conclusions-Our results document for the first time that subpressor doses of ADMA increase vascular stiffness and decrease cerebral perfusion in healthy subjects. Thus, ADMA is an important endogenous modulator of cerebral vascular tone and may be involved in the pathogenesis of cerebrovascular disease.
引用
收藏
页码:2024 / 2029
页数:6
相关论文
共 41 条
[1]   Pulse pressure and aortic pulse wave are markers of cardiovascular risk in hypertensive populations [J].
Asmar, R ;
Rudnichi, A ;
Blacher, J ;
London, GM ;
Safar, ME .
AMERICAN JOURNAL OF HYPERTENSION, 2001, 14 (02) :91-97
[2]   Impact of aortic stiffness on survival in end-stage renal disease [J].
Blacher, J ;
Guerin, AP ;
Pannier, B ;
Marchais, SJ ;
Safar, ME ;
London, GM .
CIRCULATION, 1999, 99 (18) :2434-2439
[3]  
Böger RH, 2005, ALTERN MED REV, V10, P14
[4]   CT perfusion scanning with deconvolution analysis: Pilot study in patients with acute middle cerebral artery stroke [J].
Eastwood, JD ;
Lev, MH ;
Azhari, T ;
Lee, TY ;
Barboriak, DP ;
Delong, DM ;
Fitzek, C ;
Herzau, M ;
Wintermark, M ;
Meuli, R ;
Brazier, D ;
Provenzale, JM .
RADIOLOGY, 2002, 222 (01) :227-236
[5]   RESPONSE OF CEREBRAL BLOOD-VESSELS TO AN ENDOGENOUS INHIBITOR OF NITRIC-OXIDE SYNTHASE [J].
FARACI, FM ;
BRIAN, JE ;
HEISTAD, DD .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1995, 269 (05) :H1522-H1527
[6]   Primary prevention of ischemic stroke - A statement for healthcare professionals from the Stroke Council of the American Heart Association [J].
Goldstein, LB ;
Adams, R ;
Becker, K ;
Furberg, CD ;
Gorelick, PB ;
Hademenos, G ;
Hill, M ;
Howard, G ;
Howard, VJ ;
Jacobs, B ;
Levine, SR ;
Mosca, L ;
Sacco, RL ;
Sherman, DG ;
Wolf, PA ;
del Zoppo, GJ .
STROKE, 2001, 32 (01) :280-299
[7]   Cerebral hemodynamics in a healthy population measured by dynamic susceptibility contrast MR imaging [J].
Helenius, J ;
Perkiö, J ;
Soinne, L ;
Ostergaard, L ;
Carano, RAD ;
Salonen, O ;
Savolainen, S ;
Kaste, M ;
Aronen, HJ ;
Tatlisumak, T .
ACTA RADIOLOGICA, 2003, 44 (05) :538-546
[8]   ROLE OF NITRIC-OXIDE SYNTHASE-CONTAINING VASCULAR NERVES IN CEREBROVASODILATION ELICITED FROM CEREBELLUM [J].
IADECOLA, C ;
ZHANG, FY ;
XU, XH .
AMERICAN JOURNAL OF PHYSIOLOGY, 1993, 264 (04) :R738-R746
[9]   Central and peripheral effects of asymmetric dimethylarginine, an endogenous nitric oxide synthetase inhibitor [J].
Jin, JS ;
DAlecy, LG .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1996, 28 (03) :439-446
[10]   Association between cerebrospinal fluid levels of asymmetric dimethyl-L-arginine, an endogenous inhibitor of endothelial nitric oxide synthase, and cerebral vasospasm in a primate model of subarachnoid hemorrhage [J].
Jung, CS ;
Iuliano, BA ;
Harvey-White, J ;
Espey, MG ;
Oldfield, EH ;
Pluta, RM .
JOURNAL OF NEUROSURGERY, 2004, 101 (05) :836-842