Angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II and inactive bradykinin. Several studies carried out in our laboratory have consistently identified three isoforms of ACE, at 65, 90 and 190 kDa, with the 90-kDa isoform being a possible genetic marker of hypertension. Based on these observations and the fact that nutritional stunting can be associated with hypertension, we have investigated the expression and activity of ACE in stunted children and its association with blood pressure (BP) levels and nutritional state. Sixty children aged 2-7 years were selected for this study. A urine sample was collected from each child. Angiotensin converting enzyme activity was evaluated using two different substrates, and ACE expression was detected by Western blotting. Our results show that nutritional stunting is associated with high ACE activity in childhood and that adjustment by gender does not modify the strength of this association. A greater percentage of stunted children had increased BP levels, and this clinical parameter was inversely correlated with anthropometric indicators. A greater urinary protein expression of the three ACE isoforms was observed in the group of children with growth stunting. Our findings suggest that the reported high risk of hypertension in stunted adolescents and adults are, at least partly, associated with abnormalities in the renin-angiotensin system.
The aim of this paper was to investigate the presence of the urinary 90 kDa N-domain ACE in a cohort of the population from Vitoria, Brazil, to verify its association with essential hypertension since this isoform could be a possible genetic marker of hypertension. Anthropometric, clinical, and laboratory parameters of the individuals were evaluated (n = 1150) and the blood pressure (BP) was measured. The study population was divided according to ACE isoforms in urine as follows: ACE 65/90/190, presence of three ACE isoforms (n = 795), ACE 90+ (65/90) (n = 186), and ACE 90− (65/190) (n = 169) based on the presence (+) or absence (−) of the 90 kDa ACE isoform. The anthropometric parameters, lipid profile, serum levels of uric acid, glucose, and the systolic and diastolic BP were significantly greater in the ACE 90+ compared with the ACE 90− and ACE 65/90/190 individuals. We found that 98% of individuals from the ACE 90+ group and 38% from the ACE 65/90/190 group had hypertension, compared to only 1% hypertensive individuals in the ACE 90− group. There is a high presence of the 90 kDa N-domain ACE isoform (85%) in the studied population. The percentile of normotensive subjects with three isoforms was 62%. Our findings could contribute to the development of new efficient strategy to prevent and treat hypertension to avoid the development of cardiovascular disease.
Angiotensin I-converting enzyme (ACE) plays a key role in the renin-angiotesin aldosterone cascade. We analysed the secondary structure and structural organization of a purified 65kDa N-domain ACE (nACE) from Wistar rat mesangial cells, a 90 kDa nACE from spontaneously hypertensive rats and a 130 kDa somatic ACE. The C-terminal alignment of the 65 kDa nACE with rat ACE revealed that the former was truncated at Ser(482), and the sequence of the 90 kDa nACE ended at Pro(629). Protein's secondary structure consisted predominantly of alpha-helices. The 90 and 65 kDa isoforms were the most stable in guanidine and at low pH, respectively. Enzymatic activity decreased with loss in secondary structure, except in the case of guanidine HCl where the 90 kDa fragment loses its secondary structure faster than its enzymatic activity. We identified and characterized the activity and stability of these isoforms and these findings would be helpful on the understanding of the role of nACE isoforms in hypertension.
Children with obesity have a high risk of developing cardiovascular disease and hypertension, which is associated with the renin-angiotensin system (RAS) activation and kallikrein-kinin system (KKS) inactivation. Although recent studies have identified several peptide-based biomarkers for obesity, circulating peptides from the RAS and KKS in adolescents with obesity have not been described. The aim of this study was to examine circulating levels of RAS and KKS peptides in adolescents with obesity to investigate the turnover of these peptides and their relationship to metabolic disorders resulting from weight gain. The subjects (n = 104) were divided into normal weight (NW), overweight (OW), obese (OB), and morbidly obese (MO) groups. Anthropometric profiles were created by measuring height, weight, blood pressure, and skinfolds. Plasma levels of Ang I, II, (1-7), BK, and des-Arg 9 BK were quantified by high-performance liquid chromatography. The levels were as follows:
The aim of this study was to evaluate the relationship between obesity and Sympathetic Nervous (SNS), Renin Angiotensin (RAS) and Kallikrein Kinin (KKS) Systems. Subjects were divided in groups: 43 normal weight (NW), 14 overweight (OV), 37 obese (OB) and 10 MO (MO). The Ang I, Ang II, Ang‐(1–7), Bradykinin (BK), Vasopressin (VP), norepinephrine (NE), epinephrine (EP), serotonin (SE) plasmatic levels had been measured by HPLC. Ang (1–7) levels were lower in MO and OB compared with NW (0.06±0.04; 0.24±0.17 and 0.52±0.21nmol/mL). Ang I levels were higher in MO compared with NW (0.06±0.03; 0.03±0.02). OB had higher values of VP than NW (0.107±0.0217; 0.087±0.016ng/mL). OB had higher values of EP and NE than NW (48.3±20.3 vs 34.7±17.2 and 85.6±27.9 vs 45.9±28.3 pg/mL respectively). The NW had higher concentration of SE than the OV (281.2±113.0 vs 200.1±117.1 ng/mL). MO had lower BK levels than NW (0.367 vs 0.885). Our results showed a reduction of Ang (1–7) and increased of Ang I associated with weight gain in adolescents suggesting a modulation of ACE2 and NEP. According to our results, obesity in youth seems to be related with high levels of EP, NE, blood pressure and low Ang (1–7). These alterations in the SNS, RAS and KKS, associated with low levels of Ang 1–7 and BK may contribute to the development of hypertension in obese adolescents, since these can resulting in cardiovascular target organ damage such as the heart, the vascular wall and the kidney.
The aim of this study was to evaluate the relationship between obesity and plasma Angiotensin levels [Ang I, Ang II, Ang (1–7)], Bradykinin (BK) and the presence of insulin resistance (IR). Subjects (n=104) were divided according with HOMA IR and classified as presence of RI (RI+) and absence of insulin resistance (IR−). The Ang I, Ang II, Ang (1–7), BK and Vasopressin (VP) plasmatic levels had been measured by HPLC. The RI+ group had more values of skinfolds, WHR, BMI, leucocytes, uric acid, glucose, insulin, VP, triglycerides, C reactive protein, Des Arg9‐BK, Ang I and lower plasmatic levels of Ang (1–7) and BK. Our results showed a reduction of Ang (1–7) and increased of Ang I associated with weight gain and IR in adolescents suggesting a modulation of Angiotensin Converting Enzyme 2 and Neutral Endopeptidase. Ang (1–7) and BK low levels may contribute to the development of hypertension and inflammatory conditions in obese adolescents with alterations of glucose and insulin metabolism, since these can resulting in cardiovascular target organ damage such as the heart, the vascular wall and the kidney. (Supported by Fapesp and CNPq)
Essential hypertension is a multifactorial. We aimed to investigate the prevalence of the urinary 90 kDa N‐domain ACE in a cohort of the Brazilian population from Vitória, and to verify its association with essential hypertension. A prospective study was performed to verify the presence of the urinary 90 kDa N‐domain ACE, using the Western Blotting technique. The blood pressure was also measured. The groups were divided as 1(190/65kDa); 2(190/90/65kDa) and 3(90/65kDa) according to the presence of isoform. We separate the groups in relation to blood pressure, such as hypertensive and normotensive subjects. The urine were analyzed and compared to the first phase: We note that the first and second phase group 1 remained similar (3.3%); in the second phase the group 2 presented a decrease in the percentage of cases 33.3% vs 23.3% and the 3 group showed an increase in the percentage of cases in the second phase when compared to the first part of the study (63,3% vs 73,3%). There was an increase in cases of hypertensive subjetcs in the second part of the study from 50% to 63.3%. This analysis indicated more than 90% of subjects had 90kDa ACE in their urine;The second phase shows an increased number of subjects with isoforms of 90 and 65 kDa as well as increasing the number of hypertensive subjects; 3.3% were normotensive and not express the 90kDa isoform;These data suggest a relationship between hypertension and the presence of 90 kDa ACE.
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