Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
Board

In order to characterize the effect of Nitric Oxide (NO) on isometric twitch contractions of cardiac muscle, we isolated papillary muscles(n=52) from the right ventricle of adult cats (n=42) of either sex. Each muscle was suspended in a 100 mL water jacketed organ bath filled with Krebs-Henseleit (KH)(26C;pH 7.4), gassed with 95% O2 and 5% CO2. Muscles were electrically paced 10% above threshold (70V)using a 5 ms rectangular pulse delivered at 0.2Hz. S-nitroso-N-acetylpenicillamine (SNAP)(a NO source) was added to the organ bath (0.1nM to 10µM) in a stepwise fashion. The maximal SNAP challenge increased peak isometric force (PIF) 13.3% ± 1.5% (p < 0.05,n=11) when compared to baseline values. This response was completely abolished if the muscles were equilibrated with LY83583 (1.0µM,n=5)(guanylate cyclase inhibitor) prior to the addition of SNAP. SNAP (10µM) was unable to reverse the negative inotropic action of verapamil (PIF -24.2% ± 6.9%, p < 0.05, n=5), but did reverse the negative inotropic effect of ryanodine (PIF 7.9% ± 3.7%, p < 0.05,n=5). SNAP attenuated the positive inotropic action of beta adrenergic stimmulation (10µM Dobutrex - Beta 1 agonist)(PIF -7.5% ± 1.3%, p < 0.05,n=11), and this effect was inhibited by 1.0µM LY83583(n=5). The positive inotropic effect of SNAP was reproduced using 10µM 8-Br-cGMP (PIF 7.8% ± 2.8%, p < 0.05,n=7). 8-Br-cAMP (0.1mM) and 10µM 8-Br-cGMP mimicked the SNAP induced attenuation of Dobutrex (PIF -3.5% ± 1.2%,p < 0.05,n=7). Thus NO alone produced a positive inotropic action via a cGMP induced upregulation of L-type Ca2+ channels. In combination with a cAMP agonist, NO produced a cGMP mediated negative inotropic action through an unknown mechanism.

Back to the top.
Poster Number PAreading0348
Keywords: nitric oxide, cGMP, inotropic, papillary, isometric force