title: Nitric oxide synthase inhibitor alters papillary muscle force-frequency relationship.
abstract: We provide evidence for an immediate effect of NG-monomethyl-L-arginine (L-NMMA) on the force-frequency relationship in isolated hamster papillary muscles. L-NMMA (competitive inhibitor of nitric oxide synthase) reversed the force-frequency relationship (staircase effect) in isolated hamster papillary muscles from negative to positive (P < .01; ANOVA; n = 6). The addition of L-arginine (substrate for nitric oxide synthase) blocked the L-NMMA effect (P < .01; ANOVA; n = 6). The addition of the nitric oxide (NO) donor, sodium nitroprusside (NTP), significantly increased the level of cGMP in the tissue bath (P < .01; test; n = 6) and reversed the positive inotropic effect of L-NMMA on staircase (P < .01; ANOVA; n = 6). The addition of 8-Br-cGMP to the bath resulted in a concentration-dependent decrease in tension generated by the papillary muscles (n = 6). Methylene blue (known inhibitor of cGMP) mimicked the effect of L-NMMA on staircase (P < .01; ANOVA; n = 6). L-NMMA also significantly blunted the negative inotropic effect of ryanodine (SR calcium release channel regulator) (P < .01; ANOVA; n = 6). The positive inotropic effect of Bay K 8644 (sarcolemmal, L-type calcium channel regulator) was not affected by L-NMMA (P = NS; ANOVA; n = 6). L-NMMA had no effect on either [3H]ryanodine or [3H]PN200-110 (sarcolemmal, L-type calcium channel regulator) binding to cardiac membranes. These findings support a cGMP-dependent role for endogenous NO in myocardial E-C coupling.
authors.affiliation: Department of Medicine, University of Pittsburgh School of Medicine, Pennsylvania.
authors.forename: M S
authors.initials: MS
authors.lastname: Finkel
authors.forename: C V
authors.initials: CV
authors.lastname: Oddis
authors.forename: O H
authors.initials: OH
authors.lastname: Mayer
authors.forename: B G
authors.initials: BG
authors.lastname: Hattler
authors.forename: R L
authors.initials: RL
authors.lastname: Simmons
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D006224:Cricetinae; D006152:Cyclic GMP / Q000502:physiology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D008647:Mesocricetus; D009200:Myocardial Contraction / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D019323:omega-N-Methylarginine
chemical_list: D015220:Calcium Channels; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006152:Cyclic GMP