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

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2003/03hoch011.shtml

Veröffentlicht: 11. November 2004

© 2004 Kielstein et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective

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.

Methods

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

Results

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.

Conclusions

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.