Journal article
Mechanisms Responsible for the Heterogeneous Coronary Microvascular Response to Nitroglycerin
Circulation research, Vol.68(3), pp.847-855
03/1991
DOI: 10.1161/01.res.68.3.847
PMID: 1742870
Abstract
Nitroglycerin dilates large (≥100 μm) but not small coronary arterial microvessels, and a putative metabolite of nitroglycerin, S-nitroso-l-cysteine, has been shown in vitro to dilate both large and small coronary microvessels. Based on this evidence, we tested the hypothesis that the lack of response of small coronary microvessels was due to an inability of small coronary microvessels to convert nitroglycerin into its vasoactive metabolite and examined possible explanations for this phenomenon. We studied left ventricular epicardial microvessels in vivo using video microscopy and stroboscopic epi-illumination in anesthetized, open-chest dogs. Diameters were determined while the epicardium was suffused with nitroglycerin, S-nitroso-l-cysteine, or S-nitroso-d-cysteine (all 10 μM) and nitroglycerin in the presence of l- or d-cysteine (100 μM). None of the agents affected systemic hemodynamics. Nitroglycerin dilated large arterioles (20±2%) but not small arterioles (1±1%). Both S-nitroso-l-cysteine and S-nitroso-d-cysteine were potent dilators of all size classes of microvessels. Concomitant application of l-cysteine and nitroglycerin evoked dilation in small microvessels (22±4%, p<0.5 versus nitroglycerin alone) and larger microvessels (27±6%, p=NS versus nitroglycerin alone). d-Cysteine did not alter the microvascular response to nitroglycerin in either small (7±4%, p=NS versus nitroglycerin alone) or large (18±3%, p=NS versus nitroglycerin alone) microvessels. Neither l-cysteine nor d-cysteine had a direct effect on microvascular diameter. These findings suggest that 1) sulfhydryl groups are required for the conversion of nitroglycerin to its vasoactive metabolite; 2) the interaction between nitroglycerin and sulfhydryl residues is a stereospecific process, indicating either an intracellular mechanism or a membrane-associated enzymatic reaction; and 3) a lack of available sulfhydryl groups may be responsible for the lack of response of small coronary arterioles to nitroglycerin.
Details
- Title: Subtitle
- Mechanisms Responsible for the Heterogeneous Coronary Microvascular Response to Nitroglycerin
- Creators
- Michael Kurz - Department of Internal Medicine and the Cardiovascular Center, College of Medicine, University of Iowa, Iowa City, IowaKathryn LampingJames BatesCharles EasthamMelvin MarcusDavid Harrison
- Resource Type
- Journal article
- Publication Details
- Circulation research, Vol.68(3), pp.847-855
- Publisher
- American Heart Association, Inc
- DOI
- 10.1161/01.res.68.3.847
- PMID
- 1742870
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 03/1991
- Academic Unit
- Cardiovascular Medicine; Anesthesia; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984006403402771
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