Both nitric oxide (NO) and endothelins can either increase or decrease myocardial contractility. A positive inotropic effect occurs in response to low NO concentrations, whereas a negative effect is brought about by high concentrations. Activation of protein kinase A and protein kinase G accounts for the increase and decrease in contractility respectively. Basal NO concentration is virtually unknown so that when NO-donors and NOS stimulators add newly released NO, the most frequent effect is a decrease in contractility. This negative inotropic effect represents a protection against the maladaptative activity of the increased production of angiotensin II and cathecholamines in heart failure. Unlike NO, the main effect of endothelins is an increase in contractility. While the increase in contractility is attributed to an activation of Na+/H+ and Na+/Ca2+ exchangers a decrease seems to depend on the triggering of NO-cGMP pathway by endothelin receptors B. Since endothelin concentration increases in several cardiovascular diseases, the blockade of endothelin receptors has been suggested as a therapeutic tool. The study of the endothelial-dependent repolarizing factors revealed the inotropic activity of 14,15 isoform of epoxi-eicosatrienoic acids.
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