1. Archive
2. Vol.51, No.4

Physiological Concentration of Nitric Oxide Induces Positive Inotropic Effects through cGMP Pathway in Isolated Rat Ventricular Myocytes

Abstract: We used authentic NO or NO from NO donors to show that the physiological levels of NO (<1 M) induce a positive inotropic effect and demonstrated that the effect is evoked through a cGMP-dependent pathway. In isolated rat ventricular myocytes, authentic NO at 588 nM increased both cell shortening and the intracellular Ca²⁺ ([Ca²⁺]_i) transient (133 and 117%, respectively; p< 0.05 vs. baseline), and 0.16-1.7 M NO elicited reproducible dose-dependent increases in cell shortening. NOC18 (0.1 mM: actual NO concentration 673 nM) or SNAP (0.1 mM: actual NO concentration 285 nM) showed similar effects (shortening 215% and [Ca²⁺]_i transient 160% increases, and shortening 148% and [Ca²⁺]_i transient 117% increases, respectively). The NO-induced increases in cell shortening and the [Ca²⁺]_i transient were inhibited by an inhibitor of soluble guanylate cyclase (ODQ, 30 M) or by an inhibitor of cAMP-dependent protein kinase (KT5720, 0.1 M). In the presence of an inhibitor of cGMP-inhibited cAMP-phosphodiesterase (milrinone, 10 M), NO failed to increase both cell shortening and the [Ca²⁺]_i transient. These results suggest that physiological levels of NO induce positive inotropy through a cGMP-dependent pathway.

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