Arterial versus venous metabolism of nitroglycerin to nitric oxide: A possible explanation of organic nitrate venoselectivity

John Anthony Bauer, Ho Leung Fung

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Nitroglycerin (NTG) and other organic nitrates are predominant venodilators in vivo and in vitro. This selectivity is an important determinant of their ability to relieve angina and congestive heart failure symptoms, but the mechanism of this phenomenon is unknown. Because organic nitrate vasodilation occurs through metabolism to nitric oxide (NO), we tested the hypothesis that their venoselectivity is related to an enrichment of the pertinent enzyme in venous tissue. Enzymatic conversion of NTG to NO was examined in microsomal fractions from bovine aorta as compared with vena cava tissues. NTG (150, 450, or 900 μM) was incubated with 1 mg microsomal protein and glutathione (13 μM), and cumulative NO production was measured for 5 h. When enzyme velocities were normalized to microsomal protein, statistical significance was not observed between fractions from aorta and those from vena cava. However, when enzyme activity was normalized to tissue weight or total homogenate protein, statistically higher activity was observed in the venous tissue (p < 0.05). These differences were greatest (two- to three-fold higher in vena cava at all three NTG concentrations, p < 0.01) when enzyme velocity was normalized to the initial cellular content of the homogenates (i.e., homogenate DNA concentrations). These results suggest that organic nitrate venoselectivity may be at least partly explained by enrichment of the bioactivating enzyme in venous smooth muscle cells.

Original languageEnglish
Pages (from-to)371-374
Number of pages4
JournalJournal of Cardiovascular Pharmacology
Volume28
Issue number3
DOIs
StatePublished - 1996

Keywords

  • Metabolism
  • Nitric oxide
  • Nitroglycerin
  • Organic nitrate
  • Vascular

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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