Generation of NO from molsidomine (SIN-1) in vitro and its relationship to changes in coronary vessel tone

Karsten Schrör, Stefan Förster, Isabelle Woditsch, Henning Schröder

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

The release of NO from SIN-1, the active metabolite of molsidomine, was measured in vitro in Langendorff-perfused rabbit hearts. NO in the coronary effluent was determined on-line using the oxyhemoglobin technique. Left ventricular and coronary perfusion pressure were also recorded continuously. Glyceryl trinitrate and iloprost were used as reference compounds. Infusion of SIN-1 or glyceryl trinitrate into the coronary inflow resulted in a significant and dose-dependent NO release. An apparently identical response was seen when SIN-1 was infused into the coronary effluent while the response to glyceryl trinitrate was greatly reduced or abolished. The glyceryl trinitrate-induced coronary vasodilation was only slightly diminished in presence of oxyhemoglobin whereas the response to SIN-1 was abolished. This is explained by complete scavenging of NO by oxyhemoglobin within the vessel lumen. In isolated porcine aortic endothelial cells, SIN-1 induced a significant and dose-dependent increase in cyclic GMP, whereas glyceryl trinitrate was ineffective. This would argue against biotransformation of glyceryl trinitrate to NO by endothelial cells. Finally, glyceryl trinitrate-tolerant heart preparations exhibited a considerably reduced or even undetectable release of NO, whereas the response to SIN-1 was unchanged.

Original languageEnglish (US)
Pages (from-to)S29-S34
JournalJournal of Cardiovascular Pharmacology
Volume14
StatePublished - Jan 1 1989

Keywords

  • Cyclic GMP
  • Endothelial cells
  • Glyceryl trinitrate
  • NO
  • Rabbit hearts
  • SIN-1-Molsidomine

Fingerprint

Dive into the research topics of 'Generation of NO from molsidomine (SIN-1) in vitro and its relationship to changes in coronary vessel tone'. Together they form a unique fingerprint.

Cite this