Renal interactions of renin-angiotensin system, nitric oxide and superoxide anion: implications in the pathophysiology of salt-sensitivity and hypertension.
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 reabsorption. 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.
Center for Cardiovascular Research, Prague, Czech Republic. likp@ikem.cz
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D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress; D012084:Renin-Angiotensin System; D012964:Sodium / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*; D013481:Superoxides / Q000378:metabolism*
D017673:Sodium Chloride, Dietary; D013481:Superoxides; D000804:Angiotensin II; D009569:Nitric Oxide; D012964:Sodium