Association of Urinary N-Domain Angiotensin I-Converting Enzyme with Plasma Inflammatory Markers and Endothelial Function
The aim of this study was to investigate the association between urinary 90 kDa N-domain Angiotensin I-converting enzyme (ACE) form with C-reactive protein (CRP) and homocysteine plasma levels (Hcy), urinary nitric oxide (NOu), and endothelial function (EF) in normotensive subjects. Forty healthy subjects were evaluated through brachial Doppler US to test the response to reactive hyperemia and a panel of blood tests to determine CRP and Hcy levels, NOu, and urinary ACE. They were divided into groups according to the presence (ACE90+) or absence (ACE90−) of the 90 kDa ACE, the presence (FH+) or absence (FH−) of family history of hypertension, and the presence or absence of these two variables FH+/ACE90+ and FH−/ACE90−. We found an impaired endothelial dilatation in subjects who presented the 90 kDa N-domain ACE as follows: 11.4% ± 5.3% in ACE90+ compared with 17.6% ± 7.1% in ACE90− group and 12.4% ± 5.6% in FH+/ACE90+ compared with 17.7% ± 6.2% in FH−/ACE90− group, P < 0.05. Hcy and CRP levels were statistically significantly lower in FH+/ACE90+ than in FH−/ACE90− group, as follows: 10.0 ± 2.3 µM compared with 12.7 ± 1.5 µM, and 1.3 ± 1.8 mg/L compared with 3.6 ± 2.0 mg/L, respectively. A correlation between flow-mediated dilatation (FMD) and CRP, Hcy, and NOu levels was not found. Our study suggests a reduction in the basal NO production confirmed by NOu analysis in subjects with the 90 kDa N-domain ACE isoform alone or associated with a family history of hypertension. Our data suggest that the presence of the 90 kDa N-domain ACE itself may have a negative impact on flow-mediated dilatation stimulated by reactive hyperemia.
This study was supported by FAPESP (2002/13290-2 and 2004/11149-6), We thank Vania D’Almeida, Margaret Gori Mouro, and Luciana Cristina Teixeira for their technical assistance. Thank you also to François Alhenc-Gelas, Unité 367, INSERM, Paris, France, for the kind gift of antibody Y4.
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