TY - JOUR
T1 - Nitric oxide effects on myocardial function and force-interval relations
T2 - Regulation of twitch duration
AU - Prabhu, Sumanth D.
AU - Azimi, Arshia
AU - Frosto, Teri
N1 - Funding Information:
Dr Prabhu is the recipient of an Established Investigator Grant (9740087N) from the American Heart Association. This work was also supported by a VISN-17 Grant from the Research Service of the Department of Veterans Affairs, a grant from the South Texas Health Research Center, and a grant from the San Antonio Area Foundation. The authors thank Dr Gregory Freeman for his helpful comments regarding the manuscript.
PY - 1999/12
Y1 - 1999/12
N2 - As the precise role of nitric oxide (NO) as a modulator of myocardial contraction and the force-interval relationship remains unclear, the objective of this study was to examine the effect of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) on baseline myocardial contraction, and the impact of both SNAP and the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) on the force interval relation. Studies were performed using isolated rat papillary muscles. In the presence of basiline NOS blockade, nanomolar to micromolar concentrations of SNAP exerted a modest positive inotropic effect with a small but significant increase in twitch isometric tension (P < 0.007). Nanomolar concentrations of SNAP also reduced overall twitch duration (P < 0.007). These effects were not seen in control experiments using N-acetyl-penicillamine instead of SNAP. The force-frequency response (FFR) and post-rest contractile potentiation, mechanical correlates of sarcoplasmic reticulum (SR) Ca2+ handling, were also examined. Neither L-NAME nor SNAP had any effect on post-rest potentiation following rest intervals as long as 6 min, or on the negative FFR at stimulation frequencies between 0.3 to 1.7 Hz. However, L-NAME significantly blunted the net reduction in twitch duration between 0.3 Hz and 1.7 Hz compared to control (P = 0.006), an effect reversed by 100 nM SNAP. These results indicate that low concentrations of NO can modulate myocardial function by influencing myocardial inotropy and the time course of myofilament interaction, but do not impact significantly on the force-interval relation and, by inference, SR Ca2+ handling. Moreover, modulation of twitch duration occurs over a range of stimulation frequencies, suggesting a mechanistic role for NO in the changes in contraction and relaxation time intervals seen during changes in heart rate.
AB - As the precise role of nitric oxide (NO) as a modulator of myocardial contraction and the force-interval relationship remains unclear, the objective of this study was to examine the effect of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) on baseline myocardial contraction, and the impact of both SNAP and the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) on the force interval relation. Studies were performed using isolated rat papillary muscles. In the presence of basiline NOS blockade, nanomolar to micromolar concentrations of SNAP exerted a modest positive inotropic effect with a small but significant increase in twitch isometric tension (P < 0.007). Nanomolar concentrations of SNAP also reduced overall twitch duration (P < 0.007). These effects were not seen in control experiments using N-acetyl-penicillamine instead of SNAP. The force-frequency response (FFR) and post-rest contractile potentiation, mechanical correlates of sarcoplasmic reticulum (SR) Ca2+ handling, were also examined. Neither L-NAME nor SNAP had any effect on post-rest potentiation following rest intervals as long as 6 min, or on the negative FFR at stimulation frequencies between 0.3 to 1.7 Hz. However, L-NAME significantly blunted the net reduction in twitch duration between 0.3 Hz and 1.7 Hz compared to control (P = 0.006), an effect reversed by 100 nM SNAP. These results indicate that low concentrations of NO can modulate myocardial function by influencing myocardial inotropy and the time course of myofilament interaction, but do not impact significantly on the force-interval relation and, by inference, SR Ca2+ handling. Moreover, modulation of twitch duration occurs over a range of stimulation frequencies, suggesting a mechanistic role for NO in the changes in contraction and relaxation time intervals seen during changes in heart rate.
KW - Force-interval relaion
KW - Myocardial contraction
KW - Nitric oxide
KW - Rat
KW - Sarcoplasmic reticulum
KW - Systole
KW - e-c coupling
UR - http://www.scopus.com/inward/record.url?scp=0033401799&partnerID=8YFLogxK
U2 - 10.1006/jmcc.1999.1038
DO - 10.1006/jmcc.1999.1038
M3 - Article
C2 - 10640437
AN - SCOPUS:0033401799
SN - 0022-2828
VL - 31
SP - 2077
EP - 2085
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
IS - 12
ER -