Endotheliale Dysfunktion - NO-substitution als therapeutisches prinzip

Translated title of the contribution: Endothelial Dysfunction - NO substitution as a therapeutic principle

D. Stalleicken, H. T. Schneider, H. Schröder, E. Erdmann

Research output: Contribution to journalArticlepeer-review

Abstract

Organic nitrates serve as basic therapeutics in prophylaxis and chronic therapy of coronary heart disease. They share a common metabolism via a stepwise cleavage of nitrate-ester groups. This leads to a release of nitrogen monoxide (NO), which is chemically identical to the so-called endothelium derived relaxing factor. Consequently, organic nitrates exogenously substitute any NO deficiency which may arise from an endothelial dysfunction caused by arteriosclerosis. They also share a common problem resulting from the NO release: the shifting of the cellular redox equilibrium to the oxidative side. This results in an enhanced formation of free radicals containing oxygen (the so-called reactive oxygen species, ROS). Meanwhile, ROS formation is regarded as the cause of nitrate tolerance which is for a long time known as a tachyphylaxis against the vasodilating action of organic nitrates. Interestingly, nitrate tolerance is clearly less pronounced in one representative of this class of substances than in other nitrates: pentaerythrityl tetranitrate (PETN). As a reason for this, a lesser ROS formation due to a slower NO formation is discussed. At the same time, PETN has anti-oxidative properties which help to attenuate nitrate tolerance and further undesireable drug effects resulting from this. The numerous experimental findings of recent years could be verified clinically in many instances. PETN reduces the pre-load of the ischemic myocardium thus positively affecting this substantial haemodynamic parameter. A huge multicentric clinical study on the efficacy of PETN vs. ISDN will be published soon.

Translated title of the contributionEndothelial Dysfunction - NO substitution as a therapeutic principle
Original languageGerman
Pages (from-to)342-348
Number of pages7
JournalMedizinische Welt
Volume54
Issue number12
StatePublished - Dec 1 2003
Externally publishedYes

Keywords

  • Endothelial dysfunction
  • NO substitution
  • Pentaerythrityl tetranitrate

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