The clinical pharmacology of L-arginine

被引:226
作者
Böger, RH
Bode-Böger, SM
机构
[1] Hannover Med Sch, Inst Clin Pharmacol, D-30623 Hannover, Germany
[2] Univ Clin Eppendorf, Inst Expt & Clin Pharmacol & Toxicol, D-20246 Hamburg, Germany
关键词
endothelium; nitric oxide; cardiovascular disease; pharmacokinetics; side effects;
D O I
10.1146/annurev.pharmtox.41.1.79
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
L-Arginine (2-amino-5-guanidinovaleric acid) is the precursor of nitric oxide, an endogenous messenger molecule involved in a variety of endothelium-mediated physiological effects in the vascular system. Acute and chronic administration of L-arginine has been shown to improve endothelial function in animal models of hypercholesterolemia and atherosclerosis. L-Arginine also improves endothelium-dependent vasodilation in humans with hypercholesterolemia and atherosclerosis. The responsiveness to L-arginine depends on the specific cardiovascular disease studied, the vessel segment, and morphology of the artery. The pharmacokinetics of L-arginine have recently been investigated. Side effects are rare and mostly mild and dose dependent. The mechanism of action of L-arginine may involve nitric oxide synthase substrate provision. especially in patients with elevated levels of the endogenous NO synthase inhibitor asymmetric dimethylarginine. Endocrine effects and unspecific reactions may contribute to L-arginine-induced vasodilation after higher doses. Several long-term studies have been performed that show that chronic oral administration of L-arginine or intermittent infusion therapy with L-arginine can improve clinical symptoms of cardiovascular disease in man.
引用
收藏
页码:79 / 99
页数:21
相关论文
共 146 条
[91]   L-ARGININE-INDUCED HYPOTENSION [J].
NAKAKI, T ;
HISHIKAWA, K ;
SUZUKI, H ;
SARUTA, T ;
KATO, R .
LANCET, 1990, 336 (8716) :696-696
[92]  
Noeh FM, 1996, LIFE SCI, V58, pPL131
[93]   L-arginine inhibits smooth muscle cell proliferation of vein graft intimal thickness in hypercholesterolemic rabbits [J].
Okazaki, J ;
Komori, K ;
Kawasaki, K ;
Eguchi, D ;
Ishida, M ;
Sugimachi, K .
CARDIOVASCULAR RESEARCH, 1997, 36 (03) :429-436
[94]   ACIDOSIS AND ARRHYTHMIAS IN CARDIAC-MUSCLE [J].
ORCHARD, CH ;
CINGOLANI, HE .
CARDIOVASCULAR RESEARCH, 1994, 28 (09) :1312-1319
[95]   Role of nitric oxide in the vasodilator effect of recombinant human growth hormone in patients with dilated cardiomyopathy [J].
Osterziel, KJ ;
Bode-Böger, SM ;
Strohm, O ;
Ellmer, AE ;
Bit-Avragim, N ;
Hänlein, D ;
Ranke, MB ;
Dietz, R ;
Böger, RH .
CARDIOVASCULAR RESEARCH, 2000, 45 (02) :447-453
[96]   VASCULAR ENDOTHELIAL-CELLS SYNTHESIZE NITRIC-OXIDE FROM L-ARGININE [J].
PALMER, RMJ ;
ASHTON, DS ;
MONCADA, S .
NATURE, 1988, 333 (6174) :664-666
[97]   NITRIC-OXIDE RELEASE ACCOUNTS FOR THE BIOLOGICAL-ACTIVITY OF ENDOTHELIUM-DERIVED RELAXING FACTOR [J].
PALMER, RMJ ;
FERRIGE, AG ;
MONCADA, S .
NATURE, 1987, 327 (6122) :524-526
[98]   EFFECT OF INCREASED AVAILABILITY OF ENDOTHELIUM-DERIVED NITRIC-OXIDE PRECURSOR ON ENDOTHELIUM-DEPENDENT VASCULAR RELAXATION IN NORMAL SUBJECTS AND IN PATIENTS WITH ESSENTIAL-HYPERTENSION [J].
PANZA, JA ;
CASINO, PR ;
BADAR, DM ;
QUYYUMI, AA .
CIRCULATION, 1993, 87 (05) :1475-1481
[99]  
PARDRIDGE WM, 1975, AM J PHYSIOL, V228, P1155
[100]  
PATON WDM, 1990, LANCET, V336, P1016, DOI 10.1016/0140-6736(90)92484-Y