RESUMO
OBJECTIVE: To detect the association of single polymorphisms of the renin-angiotensin-aldosterone system (RAAS), or different combinations thereof, with hypertension. DESIGN AND METHODS: The GENIPER database is the result of a collaborative effort of 13 Italian research centres to collect genomic DNA in subjects well characterized in terms of blood pressure status. A total of 2461 subjects (normotensive = 611; hypertensive = 1850) were selected and genotyped for the angiotensin-converting enzyme insertion/deletion (ACE I/D), angiotensinogen (AGT) T/C704, angiotensin receptor type 1 (AT1) A/C1166 and aldosterone synthase (ALDO) T/C-344 genetic variants. RESULTS: Allele frequencies were homogeneous over the Italian territory, with the relevant exception of the ACE I/D, the D allele being significantly less frequent in the northern region (61%) than in the rest of the country (67%; P < 0.0001). When comparing allele and genotype distributions in normotensives and hypertensives, the latter presented a small but statistically significant increase of the C allele of AGT T/C704, the A allele of AT1 A/C1166 and the T allele of ALDO T/C-344 polymorphisms (P = 0.018, P = 0.037 and P = 0.015, respectively), with similar trends all over the country. A step-wise logistic regression analysis confirmed these findings, by entering in the model as independent predictors of blood pressure status of AGT T/C704 (P = 0.013), ALDO T/C-344 (P = 0.032) and AT1 A/C1166 polymorphisms (P = 0.075), but not ACE I/D (P = 0.996). We also found some evidence of an additive effect of individual genetic variants of the RAAS, modulating at different levels the same functional pathway, on the risk of developing hypertension, but no synergistic interaction was observed. CONCLUSIONS: Our results suggest that some allelic variants of RAAS genes carry a small but identifiable risk of developing arterial hypertension.
Assuntos
Hipertensão/epidemiologia , Hipertensão/genética , Polimorfismo Genético , Sistema Renina-Angiotensina/genética , Bases de Dados Genéticas , Feminino , Frequência do Gene , Predisposição Genética para Doença/epidemiologia , Genótipo , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
OBJECTIVE: The aim of the present study was to evaluate the role of the renal nerves in the regulation of neuronal nitric oxide synthase (nNOS) gene expression in normotensive rats on different sodium balance. METHODS: Thirty-six male Sprague-Dawley rats were divided into six experimental groups combining three diets with different NaCl content (normal, 0.4%; low, 0.04%; or high, 4.0%), and bilateral renal denervation or sham denervation. After 7 days of dietary treatment, all rats were sacrificed and plasma renin activity (PRA) measured. The nNOS and renin messenger RNA (mRNA) levels in the renal cortex were determined by semiquantitative polymerase chain reaction. RESULTS: PRA was higher in animals with low sodium diet compared with those with standard diet, while it was lower in animals with high sodium diet. Renal denervation decreased PRA in normal and low sodium groups, while it did not alter the PRA values in the high sodium group. The nNOS gene expression significantly increased in rats fed with the low sodium diet compared with the standard diet group, and it significantly decreased in rats with the high sodium diet. Renal denervation significantly reduced nNOS mRNA levels in rats receiving the low sodium diet, but did not significantly influence nNOS mRNA in normal and high sodium groups. Renin mRNA was influenced by diets and denervation in a parallel way to nNOS mRNA. CONCLUSION: The renal nerves mediate the increase of renin and nNOS mRNA during sodium restriction, while the suppression of nNOS and renin gene expression during a sodium load is independent of the presence of the renal nerves. The parallel changes in renin and nNOS mRNA during different sodium intakes suggest that nNOS can be part of the complex, and still largely unclarified, macula densa mechanism of renin regulation.