Effect Of Dimethylarginine Dimethylaminohydrolase In The Development Of Salt Sensitivity

EFFECT OF DIMETHYLARGININE DIMETHYLAMINOHYDROLASE IN TEDEVELOPMENT OF SALT SENSITIVITYbySAMAR ABDULLA NASSERMay 2011Advisor: Dr. John FlackMajor: PhysiologyDegree: Doctor of PhilosophySalt sensitivity is associated with a rise in blood pressure (BP) occurring duringsodium loading and/or a fall in BP during sodium restriction that exceeds randomfluctuations in BP. Salt sensitivity is more common in African American than Caucasianhypertensives and is also present, in normotensive African Americans. The mechanismor mechanisms resulting in salt-sensitive hypertension are multiple and include bothactivation of the renin angiotensin system via increases in angiotensin II and reductionsin the endogenous vasodilator, nitric oxide (NO). An important means of NOdownregulation is through asymmetric dimethylarginine (ADMA), an endogenous NOinhibitor, which is largely metabolized by the enzyme dimethylargininedimethylaminohydrolase (DDAH). The activity of DDAH is impaired by oxidative stress,thereby permitting ADMA to accumulate thus resulting in further inhibition of NO.Increases in oxidative stress, reduction in DDAH activity, and augmented action ofADMA on depressing NO production represents a plausible mechanism in human saltsensitivity. The study investigates and characterizes the above mechanism throughwhich salt-induced depression of NO synthesis occurs in normotensive African