Low calorie diet enhances renal, hemodynamic, and humoral effects of exogenous atrial natriuretic peptide in obese hypertensives.

The expression of the natriuretic peptide clearance receptor is abundant in human and rat adipose tissue, where it is specifically inhibited by fasting. In obese hypertensives, plasma atrial natriuretic peptide (ANP) levels were found to be lower than in obese normotensives. Therefore, the increased adipose mass might influence ANP levels and/or its biological activity. The aim of the present study was to evaluate whether the humoral, hemodynamic, and renal effects of exogenous ANP in obese hypertensives might be enhanced by a very low calorie diet. Eight obese hypertensives received a bolus injection of ANP (0.6 mg/kg) after 2 weeks of a normal calorie/normal sodium diet, and blood pressure (BP), heart rate, ANP, cGMP, plasma renin activity, and aldosterone were evaluated for 2 hours before and after the injection. Diuresis and natriuresis were measured every 30 minutes. The patients then started a low calorie/normal sodium diet (510 kcal/150 mmol/d) for 4 days, and then the ANP injection protocol was repeated. The low calorie diet induced a slight weight loss (from 90.6+/-1.1 to 87. 7+/-1.2 kg; P<0.01), which was accompanied by increase of cGMP excretion (from 146.0+/-10.1 to 154.5+/-9.5 nmol/24 h; P<0.05) together with a reduction of BP (P<0.01 versus basal levels). ANP injection after diet was followed by an increase of ANP levels similar to that observed before diet, but plasma cGMP, diuresis, and natriuresis increased significantly only after diet. Similarly, the decrease of BP after ANP administration was significantly higher after diet (change in mean arterial pressure, -6.4+/-0.7 versus -4. 0+/-0.6 mm Hg; P<0.05) as well as that of aldosterone (P<0.01). These data show that a low calorie diet enhances the humoral, renal, and hemodynamic effects of ANP in obese hypertensives and confirm the importance of caloric intake in modulating the biological activity of ANP, suggesting that the natriuretic peptide system can play a role in the acute changes of natriuresis and diuresis associated with caloric restriction.

Angiotensin converting enzyme gene polymorphism and carotid atherosclerosis in a low-risk population.

OBJECTIVES: Angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism has been shown to be an independent risk factor for myocardial infarction and other cardiovascular diseases. The aim of the study was to investigate the relationship between ACE genotype and carotid atherosclerosis evaluated by ultrasonography. PATIENTS AND METHODS: ACE I/D polymorphism was determined in 240 low-risk patients (mean age 53.6 +/- 7 years) in relation to traditional risk factors and the degree of carotid atherosclerosis. Intimal-medial thickness was measured at the level of the common carotid artery, bifurcation and internal carotid on both sides. Patients were defined as normal (n = 47, intimal-medial thickness <1.0 mm), thickened (n = 56, intimal-medial thickness > or = 1.0 and < or = 1.3 mm in the thickest wall) or with an atherosclerotic plaque (n = 137, intimal-medial thickness >1.3 mm for at least one level of examination). Age, sex, body mass index, blood pressure levels and prevalence of other risk factors were similar in the three groups. I/D polymorphism was determined by polymerase chain reaction using specific primers and genomic DNA from leukocytes as template. Plasma ACE levels, plasma renin activity and plasma aldosterone were evaluated in all patients by standard procedures. RESULTS: No significant differences were found in humoral parameters, ACE, genotype distribution and the corresponding allele frequency among the three groups of patients. Only ACE plasma levels were significantly higher in the DD and ID genotypes compared with the II genotype (DD 14.27 +/- 5.05 IU/ml, ID 12.70 +/- 4.31 IU/ml; II 8.04 +/- 3.45 IU/ml). The mean intimal-medial thickness was similar in all three genotypes. CONCLUSION: Although ACE genotype has been shown to be related to coronary atherosclerosis, the present data do not indicate that the DD genotype is associated with carotid atherosclerosis. However, further studies of larger populations are needed to clarify whether genetic ACE polymorphism is associated with carotid atherosclerosis.

Plasma atrial natriuretic peptide and natriuretic peptide receptor gene expression in adipose tissue of normotensive and hypertensive obese patients.

OBJECTIVE: Human and rat adipose tissue contain very high levels of natriuretic peptides clearance receptor messenger (m)RNA, and fasting inhibits its gene expression in adipose tissue. In this study we evaluated plasma atrial natriuretic peptide (ANP) and gene expression of biologically active type A natriuretic peptide receptor (NPr-A) and clearance natriuretic peptide receptor (NPr-C) in adipose tissue of obese hypertensive and obese normotensive patients. DESIGN AND METHODS: We studied 27 untreated obese hypertensives, 26 obese normotensives (body mass index > or = 30 kg/m2), 24 non-obese essential hypertensives and 23 lean healthy subjects (body mass index < or = 25 kg/m2). Blood samples were withdrawn for ANP, plasma renin activity and aldosterone radioimmunoassays. Subcutaneous peri-umbilical adipose tissue samples were obtained, by needle aspiration, in 13 obese hypertensives and in 12 obese normotensives and used for RNA extraction. Then, complementary synthesis and semiquantitative polymerase chain reaction (PCR) with primers complementary to sequences of different exons of the genes encoding for NPr-A, NPr-C and beta-actin, were performed. 32P-labeled PCR products were separated by electrophoresis, blotted onto nylon membranes, and the exposed autoradiographic films were analysed by densitometry. NPr signals were normalized by the beta-actin expression level. RESULTS: Plasma ANP was lower in obese hypertensives than in obese normotensives (37.5+/-7 versus 43.2+/-6 pg/ml, P< 0.05), but was higher in non-obese hypertensives than in non-obese normotensives. In contrast, plasma renin activity and aldosterone were higher in the obese hypertensives. Although NPr-A and NPr-C expression were not statistically different between the two obese groups, the NPr-A: NPr-C mRNA ratios were significantly lower in obese hypertensives (P < 0.03). CONCLUSIONS: Our data suggest that in obese hypertensives compared to obese normotensives, the lower NPr-A: NPr-C ratio might determine decreased biological activity and/or an increased clearance of natriuretic peptide in adipose tissue, suggesting that the natriuretic peptide and its receptor system may be important in obesity-related hypertension where ANP levels are lower.