Renal Interactions of Renin-Angiotensin System, Nitric Oxide and Superoxide Anion: Implications in the Pathophysiology of Salt-Sensitivity and Hypertension
Abstract
Renin-angiotensin system (RAS) plays a key role in the regulation of renal function, volume of extracellular fluid and blood pressure. The activation of RAS also induces oxidative stress, particularly superoxide anion (O-2(-)) formation.
Although the involvement of O-2(-) production in the pathology of many diseases is known for long, recent studies also strongly suggest its physiological regulatory function of many organs including the kidney. However, a marked accumulation of O-2(-) in the kidney alters normal regulation of renal function and thus may contribute to the development of salt-sensitivity and hypertension.
In the kidney, O-2(-) acts as vasoconstrictor and enhances tubular sodium reabsoption. Nitric oxide (NO), another important radical that exhibits opposite effects than O-2(-), is also involved in the regulation of kidney function.
O-2(-) rapidly interacts with NO and thus, when O-2(-) production increases, it diminishes the bioavailability of NO leading to the impairment of organ function. As the activation of RAS, particularly the enhanced production of angiotensin II, can induce both O-2(-) and NO generation, it has been suggested that physiological interactions of RAS, NO and O-2(-) provide a coordinated regulation of kidney function.
The imbalance of these interactions is critically linked to the pathophysiology of salt-sensitivity and hypertension.