OBJECTIVE Heme oxygenase (HO) attenuates the production of reactive oxygen species (ROS) by its ability to degrade heme and produce carbon monoxide (CO), biliverdin/bilirubin, and to release free iron.Up-regulation of HO-1 lowers blood pressure in animals.However, the underlying mechanism is still unknown.The present study was designed to investigate whether or not up-regulation of HO-1 by the pharmacological agent hemin improves endothelial function in arteries of the spontaneous hypertensive rat (SHR).METHODS 36 weeks old SHR were divided into a hemin treatment (50 mg· kg-1, i.p., 1 d) and a control group (normal saline).Rings of aorta and mesenteric arteries were isolated for isometric tension recording, measurement of the intracellular reactive oxygen species (ROS) and prostanoids, and measurement of protein expression.RESULTS The hemin treatment augmented the expression of HO-1 in the aorta and impaired both acetylcholine-and A23187-induced endothelium-dependent contractions.ROS production was suppressed, which could be explained by a lower expression of Nox2 and COX-1 ; the production of prostacyclin was decreased, which was explained by a lower expression of COX-1 ; contractions to vasoconstrictor concentrations of prostacyclin and its mimetic iloprost were attenuated, suggesting that the responsiveness of thromboxane-prostanoid (TP) receptors to prostacyclin was decreased.The suppression of ROS and prostacyclin, as well as the decrease of TP receptors sensitivity, concur to explain the impairment of endothelium-dependent contractions caused by hemin treatment.In mesenteric arteries, hemin treatment potentiated acetylcholine-evoked relaxations attributable to endothelium-dependent hyperpolarizations (EDHF-mediated) in the presence of L-NAME and indomethacin.The IK channel blocker TRAM-34 and the Na +-K +-ATPase channel blocker ouabain significantly impaired these hemin-potentiated relaxations ; K +-mediated relaxations and expression of Na +-K +-ATPase were significantly increased by hemin treatment, explaining the improved EDHF-mediated relaxations by HO-1 induction.CONCLUSION Up-regulation of HO-1 improves endothelial function by attenuating endothelium-dependent contractions and potentiating endothelium-dependent hyperpolarizations.