Heme Oxygenase in Regulation of Renal Function and Blood Pressure

The regulation of blood pressure is dependent on multiple interacting mechanisms that influence body fluid volume, sodium balance, and vascular function. Impairments in kidney function can lead to activation of the reninangiotensin system and inappropriate sodium and fluid retention leading to hypertension. The heme-heme oxygenase system is a recently identified antihypertensive regulatory mechanism. Heme oxygenase (HO) catalyzes the conversion of heme to biliverdin, free iron and carbon monoxide (CO). Biliverdin is converted to bilirubin by biliverdin reductase and is an endogenous antioxidant. In this review, we discuss the role of HO in regulating kidney function and blood pressure in normal conditions and during hypertension. CO modulates renal vascular tone and salt transport. CO exerts renal vasodilatory effects causing an increase in renal blood flow. Induction of HO also alters expression and activity of renal heme enzymes that regulate renal hemodynamics and renal function. While HO inhibition causes an increase in blood pressure, renal HO induction attenuates the development of hypertension in several models of hypertension suggesting an important role for HO in regulation of renal function and blood pressure.