In 12 weeks old SHRs which are used in the present study, HO-1 mainly enhances eNOS activation and inhibits eNOS uncoupling to reverse endothelial premature aging; whereas in 36 weeks old SHRs, up-regulation of HO-1 reverses endothelial dysfunction via impairing endothelium-dependent contractions and enhancing endothelium-dependent hyperpolarization, without affecting NO-mediated vasodilatations [20,21]. The gene discussed is NOS3; the disease is endothelial dysfunction.