gms | German Medical Science

27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Liga zur Bekämpfung des hohen Blutdrucks – Deutsche Hypertonie Gesellschaft e. V.

26. bis 29.11.2003, Bonn

Cardiovascular effects of systemic NO synthase inhibition with asymmetric dimethylarginine in humans

Kardiovaskuläre Effekte einer systemischen NO Synthase Inhibition mit asymmetrischem Dimethylarginin beim Menschen

Meeting Abstract (Hypertonie 2003)

  • presenting/speaker J. Kielstein
  • B. Impraim
  • S. Simmel
  • S. Bode-Böger
  • D. Tsikas
  • J. Frölich
  • M. Höper
  • H. Haller
  • D. Fliser

Hypertonie 2003. 27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Bonn, 26.-29.11.2003. Düsseldorf, Köln: German Medical Science; 2004. Doc03hochV11

The electronic version of this article is the complete one and can be found online at:

Published: November 11, 2004

© 2004 Kielstein et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.




Increased blood concentrations of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) have been linked to excess cardiovascular morbidity and mortality and to progression of renal disease.


We evaluated systemic cardiovascular effects of intravenous ADMA infusion in healthy subjects using invasive techniques, i.e. right heart catheter and inulin/paraaminohippurate -clearance.


Plasma ADMA concentrations encountered in patients with cardiovascular diseases, i.e. between 2 and 10 µg/ml, caused a significant (p<0.05) decrease in plasma cGMP concentrations, the main second messenger of NO. In addition, cardiac output was significantly lower (5.3 ± 0.4 vs. 5.8 ± 0.6 l/min; p<0.05 vs. baseline), and systemic vascular resistance significantly higher (1403 ± 123 vs. 1221 ± 100 dyn.s/cm-5; p<0.05 vs. baseline). The infusion of 0.25 mg ADMA/kg/min or 3 µg L-NAME/kg/min, i.e. a potent synthetic NOS inhibitor with long action, resulted in a comparable decrease in effective renal plasma flow (from 670 ± 40 to 596 ± 29; p<0.05) and an increase in renovascular resistance (from 79 ± 5 to 90 ± 7 mmHg/ml/min; p<0.05). Moreover, administration of ADMA caused significant sodium retention and blood pressure increase (both p<0.05). The observed effects of ADMA in the systemic circulation were sustained corresponding to a mean plasma half-life of 23.5 ± 6.8 minutes, calculated from plasma ADMA decay curves in healthy subjects.


ADMA is a potent and long acting endogenous NOS inhibitor in humans. Chronically elevated ADMA blood levels may contribute to cardiovascular damage via perpetuating endothelial injury.