Abstract-Recent studies have shown that large-artery wall remodeling per se does not reduce distensibility in hypertension, indicating qualitative or quantitative changes in arterial components. The aim of the study was to determine in 1-year-old spontaneously hypertensive rats (SHRs) the changes in the elastic properties of large arteries, as assessed by the incremental elastic modulus (E inc ), and the changes in the extracellular matrix, including fibronectin (FN) and ␣5␤1-integrin. The relationship between E inc and circumferential wall stress was calculated from in vivo pulsatile changes in blood pressure and arterial diameter by using a high-resolution echo-tracking system at the site of the abdominal aorta and in vitro medial cross-sectional area. E inc -stress curves and FN and integrin ␣5-subunit contents were determined for each animal. Mean stress and E inc were higher in SHRs than in Wistar rats. However, in a common range of stress, E inc -stress curves for SHRs were superimposable on those for Wistar rats, indicating that wall materials in both strains have equivalent mechanical behavior. Immunohistochemistry indicated that total FN, EIIIA FN isoform, and ␣5-integrin increased in the SHRs aortas without changes in elastin and collagen densities. Key Words: SHR Ⅲ elastic modulus Ⅲ aorta Ⅲ fibronectin Ⅲ ␣5␤1-integrin T he mechanical properties of large arteries play a major role in cardiovascular hemodynamics through the buffering of stroke volume and the propagation of the pressure pulse.1,2 It is well recognized that mechanical properties of large arteries are primarily determined by the composition of the arterial wall. The ECM proteins, mainly collagen and elastin, influence the "passive" mechanical properties of the arterial wall whereas its "active" properties depend on the activation of VSMCs.It was generally accepted that hypertension produced an increase in large-artery stiffness.1-4 However, recent studies have shown that arterial stiffness is not increased, despite wall hypertrophy, in either hypertensive patients or SHRs. [5][6][7][8][9] This finding suggests that sustained hypertension is associated with a rearrangement of the arterial wall material, implying qualitative or quantitative changes in arterial components leading to the mechanical adaptation of the arterial wall.The elastic properties of the arterial wall material depend not only on the SMC, elastin, and collagen contents but also on the way these components are spatially organized within the media. 3,10,11 Through an interaction with specific cellular integrin receptors, FN plays an important role in cell-matrix interactions. In addition, FN may also influence VSMC phenotype.12-14 The present study was undertaken to relate the changes in the elastic properties of the arterial wall material to its composition in the ECM and to focus on FN and its specific receptor, the ␣5␤1-integrin.The interaction of specific ECM proteins with their integrin receptors has been shown to play a central role in transmitting mechanical forces to...

This study demonstrates that there is a statistically significant positive link between high heart rate and high arterial stiffness measured at the site of central and lower limb arteries. Since an elevated heart rate has been shown to be associated with cardiovascular risk, such findings may be relevant for future cardiovascular studies in epidemiology.

Abstract-We investigated the association of ␤2 adrenoceptor functional gene variants (Arg16Gly, Gln27Glu, and Thr164Ile polymorphisms), obesity phenotypes, and blood pressure levels in a large, ethnically mixed urban population. The individuals (nϭ1576) were randomly selected for a cross-sectional study of cardiovascular risk factors in Vitória, Brazil. Statistically significant associations among systolic blood pressure and the Arg16Gly and Thr164Ile variants were identified in univariate analysis. The Gly16/Gly16 genotype was still associated with systolic blood pressure (SBP) in multivariate analysis adjusting for age, gender, ethnicity, total cholesterol, diabetes, and body mass index (BMI) (Pϭ0.01). The Arg16 allele was the only genotypic variable associated with BMI, and, in a dominant model, it remained associated with an increased BMI even after adjustment for age, gender, ethnicity, triglycerides, HDL cholesterol, LDL cholesterol, diabetes, and hypertension status (Pϭ0.02). Although the different polymorphisms did not interact in the determination of SBP, a significant interaction with BMI (Pϭ0.02), not through linkage disequilibrium, was identified between the Gln27Glu and the Thr164Ile variants. Furthermore, a significant interaction among the Arg16Gly polymorphism and BMI (Pϭ0.036) and waist-hip ratio (Pϭ0.003) in determining SBP was disclosed by ANOVA factorial modeling, with SBP used as the dependent variable. An interaction between the Thr164Ile polymorphism and waist-hip ratio was also identified (Pϭ0.018). Finally, multiple logistic regression models showed a 1.48-fold increase in the risk of hypertension in individuals harboring the Gly16/Gly16 genotype and a 1.31-fold (Pϭ0.01) and a 1.49-fold (Pϭ0.003) increased risk of obesity in individuals harboring the Gln27/Gln27 genotype or the presence of the Arg16 allele, respectively. Taken together, these data provide evidence for a strong but complex relation between ␤-adrenoceptor gene variants, hypertension, and obesity.

These data have important implications for the understanding of microalbuminuria in the general population and may contribute to better ways of disease prediction and prevention.

The present study was designed to investigate the role of the autonomic nervous system in experimental hypertension induced by chronic administration of N-nitro-L-arginine methyl ester (L-NAME) in the drinking water (1 mg/mL) over 6 days. L-NAME ingestion caused a large rise in resting mean arterial pressure (MAP) (175 +/- 5 mm Hg) and heart rate (HR) (440 +/- 17 beats per minute) compared to nontreated control rats (resting MAP: 112 +/- 2 mm Hg and HR: 345 +/- 8 beats per minute). Ganglionic blockade induced by trimethaphan (5 mg/kg, intravenously) caused a significantly (P < .01) greater decrease in MAP (delta -86 +/- 7 mm Hg) compared to control rats MAP (delta -44 +/- 4 mm Hg). This strongly suggests that the level of central sympathetic tone in L-NAME-treated rats is much greater than in nontreated rats. Using atenolol and atropine alone and combined, the level of resting sympathetic drive to the heart was found to be significantly increased in L-NAME-treated rats compared to control rats. However, vagal tone to the heart was found to be virtually abolished in L-NAME-treated rats compared to control rats. These results indicate that an increase in central sympathetic drive plays an important role in the hypertension induced by chronic inhibition of nitric oxide synthesis with L-NAME.

Abstract-The genetic mechanisms underlying interindividual blood pressure variation among humans may reflect, at least in part, clustering of functional gene variants belonging to complex blood pressure control systems. In this study, we investigated the association of specific functional gene variants of the renin-angiotensin system, ACE (I/D) and angiotensinogen (M/T) genes, with blood pressure phenotypes (systolic, mean, diastolic, and pulse pressure), in an ethnically mixed urban population in Brazil. Individuals (nϭ1421) were randomly selected from the general population of the Vitoria City Metropolitan area. Neither gender, age, smoking status, total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, or diabetes was associated with ACE or AGT polymorphism in univariate analysis. No association was found between ACE variants and blood pressure phenotypes. However, a statistically significant association was revealed between the AGT 235T variant and all blood pressure phenotypes, consistent with an additive/codominant mode of action even after adjustment for age and gender (PϽ0.01). Genotypic analysis contemplating both ACE and AGT variants in the same model did not show any significant interaction between both genetic polymorphisms. In addition, the AGT 235T allele was significantly associated with hypertension in a recessive model, which remained as an independent risk factor for hypertension even after adjustment for age, gender, and ethnicity (OR, 1.33; 95% CI, 1.04 to 1.70). Taken together, these data indicate a linear relation between AGT 235T allele number (" dosage") and blood pressure in an ethnically mixed urban population and confirmed its role as an independent risk factor for hypertension for men and women when in homozygosity.

These data indicate that there is a greater pressure-dependent increase in aortic stiffness in blacks than in whites. This finding points towards major differences in mechanical properties of large arteries between these racial groups.

BackgroundCardiovascular diseases (CVD) are the main cause of death and disability in developed countries. In most cases, the progress of CVD is influenced by environmental factors and multifactorial inheritance. The purpose of this study was to investigate the association between APOE genotypes, cardiovascular risk factors, and a non-invasive measure of arterial stiffness in the Brazilian population.MethodsA total of 1493 urban Brazilian individuals were randomly selected from the general population of the Vitoria City Metropolitan area. Genetic analysis of the APOE polymorphism was conducted by PCR-RFLP and pulse wave velocity analyzed with a noninvasive automatic device.ResultsAge, gender, body mass index, triglycerides, creatinine, uric acid, blood glucose, blood pressure phenotypes were no different between ε2, ε3 and ε4 alleles. The ε4 allele was associated with higher total-cholesterol (p < 0.001), LDL-C (p < 0.001), total-cholesterol/HDL-C ratio (p < 0.001), LDL/HDL-C ratio (p < 0.001), lower HDL-C values (p < 0.001) and higher risk to obesity (OR = 1.358, 95% CI = 1.019-1.811) and hyperuricemia (OR = 1.748, 95% CI = 1.170-2.611). Nevertheless, pulse wave velocity (p = 0.66) measures were no different between genotypes. The significant association between APOE genotypes and lipid levels persisted after a 5-year follow-up interval, but no interaction between time and genotype was observed for lipids longitudinal behavior.ConclusionThe ε4 allele of the APOE gene is associated with a worse lipid profile in the Brazilian urban population. In our relatively young sample, the observed effect of APOE genotype on lipid levels was not translated into significant effects in arterial wall stiffness.