Abstract-The objective was to study oxidative status, antioxidant activities, and reactive oxygen species byproducts in whole blood and mononuclear peripherals cells and their relationship with blood pressure. Sixty-six hypertensive patients and 16 normotensive volunteers as a control group were studied. In both, whole blood and peripheral mononuclear cells oxidized/reduced glutathione ratio and malondialdehyde was significantly higher, and the activity of superoxide dismutase, catalase, and glutathione peroxidase was significantly lower in hypertensive patients when compared with normal subjects. The content of damaged base 8-oxo-2Ј-deoxyguanosine in nuclear and mitochondrial deoxyribonucleoproteins of hypertensive subjects was also significantly higher than that of the normotensive control subjects. No differences in these measurements were found among hypertensive subjects grouped in tertiles of 24-hour average mean blood pressure or between "white-coat" and established hypertensive subjects. Furthermore, no relationship was observed between the average of 24-hour mean blood pressure and oxidized/reduced glutathione ratio, reactive oxygen species byproducts, malondialdehide, or genomic 8-oxo-2Ј-deoxyguanosine. In whole blood and in mononuclear cells from hypertensive subjects, there was an increase in oxidative stress and a reduction in the activity of antioxidant mechanisms that appeared to be independent of the blood pressure values. Key Words: oxidative stress Ⅲ hypertension, renovascular Ⅲ hypertension, obesity Ⅲ risk factors Ⅲ antioxidants Ⅲ DNA O xidative stress, an excessive production of reactive oxygen species (ROS) outstripping antioxidant defense mechanisms, has been implicated in pathophysiological conditions that affect the cardiovascular system such cigarette smoking, hypercholesterolemia, diabetes, and hypertension. 1-3 Oxidative stress accompanying hypertension in animal models includes spontaneous hypertension, 4 renovascular hypertension, 5 deoxycorticosterone acetate-salt model, 6 and obesity-related hypertension. 7 Moreover, reducing superoxide radicals by infusion of superoxide dismutase (SOD) significantly decreases blood pressure in spontaneously hypertensive rats. 8 In humans, hypertension is also considered a state of oxidative stress that can contribute to the development of atherosclerosis 9 and other hypertension-induced organ damage. 10 Assessment of antioxidant activities and lipid peroxidation byproducts in hypertensive subjects indicates an excessive amount of ROS and a reduction of antioxidant mechanism activity in both blood as well as in several other cellular systems, 11 including not only vascular wall cells 12 but also those found in circulating blood. 13 Another consequence of the overproduction of ROS is the instability of critical nonlipidic macromolecules, which may have important consequences on cellular functions. Among these, genomic and mitochondrial DNA 14 are especially relevant. Up to now, however, no information concerning the damage of both types of DNA in ce...

Abstract-We evaluated the association between salt-sensitive hypertension and 3 different genetic polymorphisms of the renin-angiotensin system. Fifty patients with essential hypertension were classified as salt sensitive or salt resistant, depending on the presence or absence of a significant increase (PϽ0.05) in 24-hour ambulatory mean blood pressure (BP) after high salt intake. Key Words: angiotensin-converting enzyme Ⅲ genes Ⅲ angiotensin II Ⅲ blood pressure monitoring, ambulatory T he blood pressure (BP) response to increased dietary salt is heterogeneous among individuals, a phenomenon known as salt sensitivity. Normotensive and hypertensive salt-sensitive subjects tend to exhibit familial history of hypertension more frequently than salt-resistant subjects. 1,2 This suggests the existence of genetic determinants that influence BP sensitivity to sodium chloride. More than 10 years ago, Weinberger et al 3 reported a significant relation between haptoglobin 1-1 phenotype and BP response to intravenous sodium overload both in normotensive and hypertensive subjects.The renin-angiotensin system (RAS) has a central role in controlling BP and sodium homeostasis. 4 In the last decade, several authors have investigated RAS polymorphisms as genetic determinants of essential hypertension and end-organ damage. Although the results obtained are controversial, the presence of the D allele in intron 16 of the angiotensinconverting enzyme (ACE) gene appears to be associated with a higher risk for development of both macrovascular and microvascular disease in hypertensive individuals. 5 Moreover, the presence of the T allele in exon 2 of the angiotensinogen (AGT) gene appears to be associated with a higher risk for development of hypertension. 6 Finally, the association of the T allele of the AGT gene and the D allele of the ACE gene has a synergistic effect on the incidence of cerebrovascular disease, 7 and the association of the D allele of the ACE gene and the C allele of angiotensin II type 1 (AT1) receptor gene appears to increase the risk of myocardial infarction. 8 The RAS also is implicated in the BP response to salt intake. Low-renin hypertensives show an increased BP response to NaCl load, 9 and salt-sensitive individuals exhibit a blunted response of the RAS when they switch from low to high salt intake compared with salt-resistant subjects. 10 Moreover, plasma levels of ACE and angiotensinogen differ in subjects with different ACE and angiotensinogen genotypes. 11,12

Abstract-We analyzed the association between salt sensitivity in essential hypertension and 8 genetic polymorphisms in 6 genes of the renin-angiotensin aldosterone system. Seventy-one patients with essential hypertension were classified as salt sensitive or salt resistant by means of the 24-hour ambulatory blood pressure (BP) change to high salt intake. The polymorphisms evaluated correspond to the following genes: ACE (I/D), angiotensinogen (M235T), angiotensin II type 1 receptor (A1166C), 11␤-Hydroxysteroid dehydrogenase type 2 (11␤HSD2) (G534A), aldosterone synthase (C-344T and Intron 2 conversion), and the mineralocorticoid receptor (G3514C and A4582C); all were determined using standard polymerase chain reaction methods. Thirty-five patients (49%) were classified as salt sensitive. We analyzed the BP response to high salt intake among genotypes and found a significant association for ACE I/D and 11␤HSD2 G534A polymorphisms. Patients homozygous for the insertion allele of the ACE gene (II) had a significantly higher BP increase with high salt intake than did patients homozygous for the deletion allele (DD). Heterozygous patients (ID) exhibited an intermediate response. The prevalence of salt-sensitive hypertension was also significantly higher (Pϭ0.003) in II (68%) and DI patients (59%) compared with DD hypertensives (19%). With respect to 11␤HSD2 G534A, patients with the GG genotype had a significantly higher systolic BP increase with high salt intake than did GA patients. In addition, plasma renin activity suppression in response to high salt was significantly greater in GA patients than in GG patients. The prevalence of salt-sensitive hypertension was 14.3% in GA patients and 50.8% in GG patients (Pϭ0.067). In conclusion, the I allele of ACE I/D polymorphism is significantly associated to salt-sensitive hypertension. The BP response to high salt intake was different among genotypes of ACE I/D and 11␤HSD G534A, suggesting that these polymorphisms may be potentially useful genetic markers of salt sensitivity.