Biphasic nature of inotropic action of nitric oxide donor NOC7 in guinea-pig ventricular trabeculae.
The effects of nitric oxide (NO) donor on the contractility of guinea-pig ventricular trabeculae were explored to clarify whether NO affects the function of sarcoplasmic reticulum (SR) and the contractile elements. NO donor, 3-(2-hydroxy-1-methyl-2-nitroso-hydrazino)-N-methyl-1-propanamine (NOC7), increased monotonically the amplitude of the twitch tension induced by electrical stimulation at a concentration of 20 microM. A higher concentration of NOC7 (200 microM) caused a biphasic response: transiently increased the amplitude of twitch and then decreased it. On wash-off of the higher concentration of NOC7, a rebound increase of the twitch amplitude was observed. An inhibitor of NO-sensitive guanylyl cyclase, 1H-[1,2,4]oxadiazolo-[4, 3-a]quinoxalin-1-one (ODQ), abolished the mono-tonic increase and rebound increase in the amplitude of tension but did not affect the decrease in the amplitude of tension at the higher concentration of NOC7. Oscillatory contractions developed by beta-escin-skinned muscle fibers were not changed by NOC7 at either concentration. Caffeine-induced tension transients indicating the Ca(2+)-accumulating and -releasing functions of intracellular Ca(2+) stores were not affected by NOC7. NOC7 did not change the steady tension developed in 1.6 microM Ca(2+) containing solution with and without ODQ. These results suggest that the biphasic inotropic effects by NOC7 were not caused by modifying the function of SR and the Ca(2+) sensitivity of myofilaments of the guinea-pig ventricular trabecula, but at least the positive inotropic effect was mediated through cGMP-dependent mechanisms.
Ohba
M
M
Department of Physiology, Faculty of Medicine, Fukuoka University, Fukuoka, 814-0180, Japan. mohba@msat.fukuoka-u.ac.jp.
Kawata
H
H
D000818:Animals; D005260:Female; D006168:Guinea Pigs; D006652:Histological Techniques; D006834:Hydrazines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D016276:Ventricular Function / Q000187:drug effects*
C115239:3-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-propanamine; D006834:Hydrazines; D020030:Nitric Oxide Donors