Negative effect of nitric oxide on shorteningfrequency relationship in cardiac myocytes is diminished after simulated ischemia-reperfusion |
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Authors: | Weiss Harvey R Gandhi Ankur Scholz Peter M |
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Institution: | (1) Department of Physiology and Biophysics, UMDNJ—Robert Wood Johnson Medical School, 675 Hoes Lane Piscataway, NJ 08854-5635, USA |
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Abstract: | Increasing stimulation rate increases function in cardiac
myocytes and nitric oxide and cyclic GMP inhibit this effect. We
tested the hypothesis that myocyte stunning would blunt both the
effects of increases in rate and of nitric oxide and cyclic GMP.
Ventricular myocytes from 11 rabbits were used to determine
maximum rate of shortening (Rmax, µm/s)
and %shortening during control and after simulated ischemia 15
min 95% N2- 5%
CO2] and reperfusion reoxygenation].
Measurements were obtained at 1–4 Hz with vehicle,
1H1,2,4]oxadiazolo4,3,alpha] quinoxaline-1-one (ODQ)
10–6 M, soluble guanylyl cyclase
inhibitor, or NG-nitro-L-arginine
methyl ester, nitric oxide synthase inhibitor (L-NAME)
10–5 M. In control, increases in rate
increased Rmax from 69 ± 3 to 254±12 and
%shortening from 5.3 ± 0.3 to 8.7 ± 0.5. Both ODQ and L-NAME shifted
values higher. With stunning, the effects of pacing on Rmax and
%shortening were blunted and ODQ and L-NAME failed to alter
these values. Cyclic GMP was 322±37
pmol/105 myocytes at baseline and
these values were lowered by ODQ (244 ± 31) and LNAME (207 ± 23),
and similar changes were observed in stunned myocytes.
Increasing frequency increased function, and reducing nitric
oxide/cyclic GMP enhanced this relationship. The effect of
nitric oxide was diminished by stunning, but this was not
related to altered cyclic GMP levels. This suggested changes in
effects of cyclic GMP downstream to its production during
myocardial stunning. |
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Keywords: | Ischemia-reperfusion myocardial stunning cyclic GMP heart rate-shortening rabbit |
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