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Coronary hemodynamics in endothelial NO synthase knockout mice
A Gödecke1, U K Decking, Z Ding
1Institut für Herz- und Kreislaufphysiologie, Heinrich-Heine-Universität, Düsseldorf, Germany. axel@herzkreis.uni-duesseldorf.de
Circulation Research
|February 19, 1998
Summary
Mice lacking endothelial NO synthase (eNOS) were hypertensive but showed normal coronary flow, indicating compensatory mechanisms. Acetylcholine-induced vasodilation in these mice was mediated by prostaglandins, not eNOS.
Area of Science:
- Cardiovascular Physiology
- Vascular Biology
- Nitric Oxide Signaling
Background:
- Endothelial NO synthase (eNOS) plays a critical role in regulating vascular function.
- Understanding the specific contribution of eNOS to coronary hemodynamics is essential for cardiovascular health.
- Previous studies suggest NO mediates vasodilation, but its role in basal tone and reactive hyperemia requires further elucidation.
Purpose of the Study:
- To investigate the specific function of eNOS in the coronary vasculature using a genetically modified mouse model.
- To determine the role of eNOS in basal coronary flow, reactive hyperemia, and responses to acetylcholine.
- To explore compensatory mechanisms in eNOS-deficient mice and the involvement of prostaglandins in vasodilation.
Main Methods:
- Generation of eNOS-deficient (eNOS-/-) mice and Western blot/immunohistochemical validation of eNOS absence.
- Measurement of NOx formation in aortic endothelial cells.
- Analysis of coronary hemodynamics in Langendorff-perfused hearts under basal and stimulated conditions.
- Pharmacological inhibition of NOS with L-NAME and cyclooxygenase with diclofenac.
Main Results:
- eNOS-/- mice exhibited hypertension without cardiac hypertrophy.
- Basal coronary flow and reactive hyperemia were not different between eNOS-/- and WT mice, suggesting compensatory mechanisms.
- Acute NOS inhibition in WT hearts reduced basal flow and reactive hyperemia.
- Acetylcholine induced vasoconstriction followed by vasodilation in WT, with L-NAME reducing vasodilation; eNOS-/- hearts showed augmented initial vasoconstriction but unaffected vasodilation.
- Prostaglandins mediated acetylcholine-induced vasodilation in both WT and eNOS-/- mice.
Conclusions:
- Acute eNOS inhibition highlights NO's role in basal coronary tone, reactive hyperemia, and acetylcholine response.
- Chronic absence of eNOS leads to compensatory mechanisms preserving basal coronary flow and reactive hyperemia.
- Prostaglandins are the primary mediators of acetylcholine-induced vasodilation in the coronary vasculature, irrespective of eNOS status.