Rodent studies employing the broad-spectrum NADPH oxidase inhibitor apocynin, or mice genetically engineered to lack Nox2 or Nox4, reveal that NADPH oxidase is a key contributor to the oxidative stress associated with VH/HF, and that suppression of NADPH oxidase activity substantially ameliorates this syndrome; likewise, activation of Nox2 in coronary endothelium leads to coronary endothelial dysfunction in VH/HF models [87,113,114,115,116,117,118,119,120]. This evidence concerns the gene NOX4 and hydrops fetalis.