Cardiovascular Diseases Poster Session
Barclay, JK. (Department of Human Biology & Nutritional Science, University of Guelph, Canada)
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 10ÁM) 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 (1.0ÁM,n=5)(guanylate cyclase inhibitor) prior to the addition of SNAP. SNAP (10ÁM) 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 (10ÁM Dobutrex - Beta 1 agonist)(PIF -7.5% ▒ 1.3%, p < 0.05,n=11), and this effect was inhibited by 1.0ÁM LY83583(n=5). The positive inotropic effect of SNAP was reproduced using 10ÁM 8-Br-cGMP (PIF 7.8% ▒ 2.8%, p < 0.05,n=7). 8-Br-cAMP (0.1mM) and 10ÁM 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.
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|Reading, S.; Barclay, JK.; (1998). Nitric Oxide Modulates Contractility in Feline Cardiac Muscle. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Available at URL http://www.mcmaster.ca/inabis98/cvdisease/reading0348/index.html|
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