Taking into account the above-mentioned effects of relaxin-2 and given that endothelin-1 is one of the most potent vasoconstrictor neurohormonal factors involved in the pathophysiology of HF and PAH [109,110], and that endothelin-1 plasma levels are elevated during HF [100], it is conceivable that relaxin-2 is increased in PAH and HF with right-sided heart pressure overload as a compensatory protector mechanism against the pathologically increased activation of the vasoconstrictor mediators endothelin-1 and angiotensin (Ang) II [70,91,108]. This evidence concerns the gene RLN2 and hydrops fetalis.