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Old 11-13-2017, 07:20 AM
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rss Associations between asymmetric dimethylarginine (ADMA), nitrite-dependent renal carb

Associations between asymmetric dimethylarginine (ADMA), nitrite-dependent renal carbonic anhydrase activity and plasma testosterone levels in hypogonadal men.

Hellenic J Cardiol. 2017 Nov 08;:

Authors: Tsikas D, Kinzel M

Abstract
BACKGROUND: Circulating inorganic nitrite (NO2(-)) is an abundant nitric oxide (NO) reservoir. Renal carbonic anhydrase (CA) mediates the absorption of urinary nitrite. The urinary nitrate-to-nitrite molar ratio UNOxR is a measure of nitrite-dependent renal CA activity. The CA family is also involved in the bioactivation of nitrite to S-nitrosothiols and NO. Thus, CA isoforms may combat atherosclerosis.
METHODS: In plasma and urine of ten hypogonadal men we measured the major NO metabolites nitrite and nitrate, and the endogenous inhibitor of NO synthase (NOS) asymmetric dimethylarginine (ADMA) before and after a 24-weeks testosterone treatment to normalize plasma testosterone levels. We tested potential correlations between plasma testosterone, ADMA and UNOxR.
RESULTS: Baseline UNOxR levels were low, indicating impaired nitrite-dependent renal CA activity. Baseline plasma testosterone levels correlated inversely with creatinine-corrected urinary nitrite excretion (r=-0.74, P=0.036) and positively with UNOxR (r=0.72, P=0.044). Plasma testosterone levels normalization deteriorated these correlations. At baseline UNOxR correlated inversely with urinary excretion of ADMA (r=-0.75, P=0.013). Plasma testosterone levels normalization did not affect UNOxR. Secondary and primary hypogonadal hypogonadism men differed with respect to baseline biomarker levels and to the testosterone effects.
CONCLUSIONS: Impaired testosterone synthesis in hypogonadal men favors inflammatory processes, elevates inducible NOS-mediated NO formation, and impairs CA-dependent nitrite reabsorption. Normalization of plasma testosterone reverses these processes. Pharmacological testosterone may combat atherosclerosis in hypogonadal hypogonadism.


PMID: 29128547 [PubMed - as supplied by publisher]



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