Differential biotransformation of glyceryl trinitrate by red blood cell-supernatant fraction and pulmonary vein homogenate

Canadian Journal of Physiology and Pharmacology
G S MarksJ F Brien

Abstract

We have demonstrated previously that glyceryl trinitrate (GTN) undergoes biotransformation to two glyceryl dinitrate (GDN) metabolites in the human red blood cell-supernatant fraction (RBC-SF) by hemoglobin-mediated and sulfhydryl-dependent enzymatic mechanisms. In the present study, we have shown that biotransformation of GTN in rabbit RBC-SF yields a glyceryl-1,2-dinitrate (1,2-GDN)/glyceryl-1,3-dinitrate (1,3-GDN) ratio of 5.3. Following inhibition of hemoglobin-mediated biotransformation of GTN by carbon monoxide (CO), the 1,2-GDN/1,3-GDN ratio was 2.1. Following inhibition of sulfhydryl-dependent biotransformation by N-ethylmaleimide (NEM), the 1,2-GDN/1,3-GDN ratio was 30.0. We have demonstrated previously that for GTN-induced vasodilation of isolated bovine pulmonary vein (BPV), the 1,2-GDN/1,3-GDN ratio was 7.1, which indicated that a hemoprotein-dependent process was involved in GTN biotransformation. To determine if this was the case, the biotransformation of GTN (0.51 microM) was studied in BPV homogenates; 31.1 pmol GDN/mg BPV protein was formed in 20 min. The 1,2-GDN/1,3-GDN ratio was 1.1, which indicated that hemoprotein-mediated biotransformation did not occur. This conclusion was supported by the fact that CO di...Continue Reading

Citations

Feb 27, 2003·Clinical Pharmacokinetics·Satoru Hashimoto, Atsuko Kobayashi
Apr 12, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Nelson N OrieKevin P Moore
Nov 14, 2003·Canadian Journal of Physiology and Pharmacology·Mark A BustardGraeme N Smith
Jul 1, 1994·Trends in Pharmacological Sciences·B M BennettW C Simon

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antianginal Drugs: Mechanisms of Action

Antianginal drugs, including nitrates, beta-blockers, and calcium channel blockers, are used in the treatment of angina pectoris. Here is the latest research on their use and their mechanism of action.