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Nitric oxide attenuates cardiac myocyte contraction
A J Brady1, J B Warren, P A Poole-Wilson
1Department of Cardiac Medicine, National Heart and Lung Institute, London, United Kingdom.
Insights
Nitric oxide (NO) can decrease cardiac myocyte contractility. This finding is significant because cardiac cells are very close to blood vessels, suggesting NO
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
- Endothelial Function
Background:
- Cardiac muscle fibers are closely associated with microvessels.
- Endothelial-derived factors may influence cardiac myocyte function.
Purpose of the Study:
- To investigate the effects of nitric oxide (NO) and related compounds on cardiac myocyte contractility.
- To determine the mechanism by which NO affects cardiac myocytes.
Main Methods:
- Experiments using isolated, electrically stimulated guinea pig cardiac myocytes.
- Endothelium-myocyte co-culture systems.
- Application of bradykinin, nitrovasodilators, NO solutions, and cyclic GMP analogs.
Main Results:
- Bradykinin reduced myocyte shortening, an effect blocked by NG-nitro-L-arginine methyl ester.
- Sodium nitroprusside and NO solutions attenuated myocyte contraction amplitude.
- The effects of NO were reversed by methylene blue and mimicked by 8-bromoguanosine 3',5'-cyclic monophosphate.
Conclusions:
- Nitric oxide (NO) attenuates cardiac myocyte contractility.
- NO appears to mediate its effects through the production of intracellular guanosine 3',5'-cyclic monophosphate (cGMP).
- Endothelial-derived NO may play a significant role in regulating myocardial function due to the close proximity of myocytes to capillaries.
Abstract:
Cardiac muscle fibers have microvessels in close proximity, the distance from the nearest capillary being no greater than 8 microns. We performed experiments on isolated, electrically stimulated, contracting guinea pig cardiac myocytes to test whether NO from endothelium or nitrovasodilators or directly superfused in solution might affect myocyte contractility. In endothelium-myocyte coculture experiments, 10(-7) M bradykinin reduced myocyte shortening by 11 +/- 3.5%. This effect was abolished in the presence of NG-nitro-L-arginine methyl ester and was unaffected by indomethacin. Sodium nitroprusside, but not organic nitrovasodilators, reduced myocyte contraction amplitude by 23% at 3 x 10(-5) M. This effect was reversed by methylene blue. Superfusion with NO solution had an effect similar to sodium nitroprusside, as did exposure to 8-bromoguanosine 3',5'-cyclic monophosphate. Thus the present study shows that cardiac myocyte contraction is attenuated by NO, which appears to act via production of guanosine 3',5'-cyclic monophosphate within the myocytes. Because cardiac myocytes in vivo are in such close proximity to endothelium, the effects of endothelial products on cardiac myocyte contractility may be important in myocardial function.