Hypertension in relation to nitric oxide, asymmetric dimethylarginine, and inflammation: Different patterns in heart transplant recipients and individuals with essential hypertension

Most heart transplant (HTx) recipients develop hypertension, characterized by increased peripheral vascular tone and endothelial dysfunction. Reduced levels of nitric oxide (NO) have been found in essential hypertension, and herein we investigated the possible role of altered concentrations of NO in posttransplant hypertension. Plasma levels of the NO-derived end products NO2(-) + NO3(-), the endogenous inhibitor of NO synthase asymmetric dimethylarginine (ADMA), and the inflammatory cytokine tumor necrosis factor (TNF)-alpha were examined in 65 stable hypertensive long-term (6 years [range 1-13]) survivors of HTx. HTx recipients were compared with 39 individuals with essential hypertension and 25 normotensive controls. RESULTS Hypertensive HTx recipients had raised NO2(-) + NO3(-) levels in plasma, positively correlated with 24-hour mean blood pressure (BP). In contrast, individuals with essential hypertension had decreased NO2(-) + NO3(-) concentration comparing controls, inversely correlated with 24-hour mean BP. Moreover, although TNF-alpha levels were significantly raised in HTx recipients compared with both healthy controls and individuals with essential hypertension, it was positively correlated to 24-hour BP and NO2(-) + NO3(-). Although only a slight increase was found in essential hypertension, no correlations were found in these nontransplant individuals. Finally, although asymmetric dimethylarginine (ADMA) tended to be raised in essential hypertension, this endogenous nitric oxide synthase (NOS) inhibitor was significantly decreased in HTx recipients compared with normotensive controls. Our findings suggest that different mechanisms may be operating in the pathogenesis of posttransplant compared with essential hypertension, with persistent inflammation, raised NO2(-) + NO3(-), and decreased ADMA levels characterizing the former group.