A comparative study of plasma renin activity, aldosterone and atrial natriuretic hormone between normotensive and hypertensive people living at below sea level altitude (Jordan Valley) and those residing at moderate altitude above

A cross-sectional study was designed to investigate the association of the levels of plasma renin activity (PRA) and aldosterone (ALDO) and atrial natriuretic hormone (ANH) with the rates of hypertension prevalence in people living at 340 meters below sea level, the Jordan Valley (JV) and those residing at 620 meters above sea level, Irbid City. 1072 natives from the JV and 1402 natives from Irbid City were covered by a questionnaire to estimate hypertension prevalence in the JV and Irbid city (population age: 35-65 years). Male subjects were selected from the JV (24 hypertensives, 46+/-15 years old, and 93 normotensives, 33+/-13 years old) and from Irbid City (31 hypertensives, 47+/-12 years old, and 89 normotensives, 40+/-13 years old) to evaluate the levels of PRA, ALDO and ANH. Hypertension was less common in the JV than in Irbid City (9.9% vs. 13.6%). The levels of PRA in the hypertensive subjects compared to the normotensive subjects were lower in the JV (1.7+/-1.0 vs. 2.6+/-1.4 ng/ml/hr) but were similar in Irbid City (2.9+/-2.7 vs. 3.2+/-2.7). The levels of ALDO in the hypertensive subjects compared to the normotensive subjects were similar in the JV (119+/-58 vs. 139+/-66 pg/ml) but were higher in Irbid City (199+/-112 vs. 146+/-84). The levels of ANH in the hypertensive subjects compared to the normotensive subjects were lower in the JV (13.9+/-9.3 vs. 28.0+/-12.7 ng/ml) and were also lower in Irbid City (21.0+/-12.2 vs. 26.7+/-11.6).     

Blunting of circadian rhythms and increased acrophase variability in sleep-time hypertensive subjects

24 h and ultradian rhythms of blood pressure (BP) have been previously shown to be disorganized in nocturnal hypertensive subjects. The present study was undertaken to further analyze the ultradian and circadian BP rhythm structure in sleep-time hypertensive subjects with normal or elevated awake-time BP levels. Fourier analysis was used to fit 24, 12, 8, and 6 h curves to mean BP as well as heart rate (HR) time series data derived from 24 h ambulatory blood pressure monitoring. Awake and sleep periods were defined according to individual sleep diaries. Awake-time hypertension was defined as diurnal systolic (SBP) and/or diastolic BP (DBP) means ≥135/85 mmHg. Sleep-time hypertension was defined as nocturnal SBP and/or DBP means ≥120/70 mmHg. The sample included 240 awake-time normotensive subjects (180 sleep-time normotensives and 60 sleep-time hypertensives) and 138 untreated awake-time hypertensive subjects (31 sleep-time normotensives and 107 sleep-time hypertensives). The amplitude and integrity (i.e., percent rhythm) of the 24 and 12 h BP rhythms were lower in the sleep-time hypertensive subjects and higher in the awake-time hypertensive subjects. However, no differences were detected when the integrity and amplitude of the 6 and 8 h mean BP rhythms were analyzed. The sleep-time hypertensive group showed significantly higher 24 h BP rhythm acrophase variability. No differences could be found in any of the HR rhythm parameters. Altogether, the findings suggest a disorganization of the BP circadian rhythm in sleep-time hypertensives that results in reduced 24 h rhythm amplitude and integrity that could be related to cardiovascular risk.     

Changes in carbonic anhydrase may be the initial step of altered metabolism in hypertension

Carbonic anhydrase (CA) is a well characterized pH regulatory enzyme in most of the tissues in the body. Changes in activities of CA have been associated with altered metabolism, especially in diabetes mellitus. Insulin resistance and hyperinsulinemia are common in hypertension. To investigate the possible role of CA, we measured the CA activity spectrophotometrically using p-nitrophenyl acetate as a substrate and acetazolamide, the specific inhibitor, in erythrocytes from normotensive and essential hypertensive subjects. Further, to evaluate the insulin action on CA, we used two different hemolysates; (i) insulin applied into hemolysate and (ii) hemolysate from insulin treated erythrocytes in vitro before the determination of CA activity. Two different levels of CA activities were obtained in these patients. CA activities were much lower (mean +/- SD, 0.88 +/- 0.19 U/min/mL) and higher (mean +/- SD, 1.77 +/- 0.23 U/min/mL) in patients than the normotensive controls (mean +/- 1 SD, 1.41 +/- 0.1 U/min/mL). These differences in both the groups were statistically significant (p less than 0.001). Similarly, total esterase activities in patients were (1.41 +/- 0.27 U/min/mL) that was 30% less in low activity group and (2.47 +/- 0.25 U/min/mL) that was 22% more in higher activity group in comparison with those from normotensives (2.02 +/- 0.17 U/min/mL). The relative percent of CA activities of insulin treated erythrocytes from normotensives and hypertensives were 11% and 18% higher than without insulin (p less than 0.05). No difference was observed when insulin was applied in the hemolysate. We conclude that essential hypertensive patients are associated with altered CA activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Impaired glucose metabolism in hypertensive patients

We have studied glucose tolerance under carefully controlled conditions in 79 patients with arterial hypertension. The results show that, in patients with arterial hypertension but without clinical diabetes mellitus, the glucose tolerance was abnormal in 77.3% and normal in 22.3%. The corresponding figure in the control group of normotensive subjects was 0%. In each test the responses to glucose administration were analyzed by plotting the logarithm of the blood glucose concentration against time. For the points between 60 and 120 min, corresponding to the periods following glucose administration, a linear relationship was obtained and showed a decline at an exponential rate, as noted by other observers. An estimate of the volume of distribution of glucose was obtained as follows. Values observed in hypertensives with a pathological percent fall in blood glucose per minute (Kg) were 29.8 +/- 12.0 (mean +/- SD) liters and those in normal subjects with normal Kg values had a mean of 14.35 +/- 2.98, the difference being highly significant (p less than 0.0001). The results of the theoretical glucose concentration are also presented. Those obtained from subjects with normal Kg values (359.0 +/- 58.4 mg/dl) are significantly higher than in subjects with pathological Kg values (257.6 +/- 51.3 mg/dl; p less than 0.0001). All patients with either pathological or normal Kg values had normal glucose concentration levels, fasting blood sugar and no glucose in the urine specimen. The difference between pathological Kg values (107.0 +/- 25.8 mg/dl) and normal Kg values (90.6 +/- 13.0 mg/dl) was not found to be statistically different (p greater than 0.05). The distribution and means of glucose half time in controls with normal Kg values and hypertensives with pathological Kg values were: 63.5 +/- 11.5 and 137.8 +/- 48.1 min, respectively. The difference between normal and pathological Kg values being statistically significant at a confidence level above 99.5%. We also studied the free glucose pool at zero time. A significantly higher level was found in hypertensives with pathological Kg values, again indicating an impairment in glucose metabolism in this group: 90.6 +/- 26.5 vs. 65.0 +/- 5.4 g (p less than 0.0001). Another study showed an estimate of the mean cellular glucose uptake (MCUg) per minute and per kilogram body weight. The MCUg following glucose loading decreased considerably in hypertensives with pathological Kg values. The percentage reduction ranged between 50 and 55% hypertensives with pathological Kg values 4.1 +/- 0.8, and normotensives with normal Kg values, 8.0 +/- 0.6 (p less than 0.0001).(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of plasma from essential hypertensives on vascular tone of aortic strips, isolated perfused mesentery and isolated perfused kidney

Different vascular models of normotensive Wistar rats, including aortic strips, isolated perfused mesentery and isolated perfused kidney, were used to study hemodynamic effects of plasma fractions obtained by gel filtration from the blood of essential hypertensive and normotensive subjects. Plasma fractions from essential hypertensives studied had been shown to increase blood pressure after intravenous injection in rats. In the aortic strips, 50 microliters of a hypertensive fraction (HF) elicited a calcium-dependent contraction of 0.14 +/- 0.035 mN (n = 20, p less than 0.05), which was inhibited by nifedipine, whereas tension of the strips was not significantly changed by normotensive fractions (NF) (n = 17). In the isolated perfused mesentery preparation, no significant change of perfusion pressure by HF or NF could be demonstrated (n = 10). In the isolated perfused kidney, a transient increase of perfusion pressure was induced by HF (19.5 +/- 16.6 mm Hg, n = 40, P less than 0.001) but not by NF. This increase was abolished in calcium-free, 2 mmol/l EGTA containing perfusion medium. The response was diminished, but not abolished by nifedipine. These data demonstrate vasopressor properties of plasma from essential hypertensives, which might be the consequence of a circulating vasoconstrictor substance in the blood of essential hypertensives.     

Abnormal response of urinary eicosanoid system to norepinephrine infusion in patients with essential hypertension.

To define the role of the renal eicosanoid system in sustaining renal homeostasis in hypertension, we investigated the alterations in urinary excretions of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), a stable metabolite of vasodepressor prostacyclin, and thromboxane B2 (TXB2), a stable metabolite of vasoconstrictor TXA2, when norepinephrine was continuously infused for 90 min in hypertensive (n = 13) and normotensive subjects (n = 14). There was no difference in plasma norepinephrine concentration after the infusion between the hypertensive and the normotensive subjects. Moreover, the percent changes in renal vascular resistance elicited by norepinephrine in the hypertensives were equal to those of the normotensive subjects. In the normotensive subjects, the norepinephrine infusion significantly increased urinary 6-keto-PGF1 alpha excretion and decreased urinary excretion of TX, both of which are beneficial for sustaining renal function. In fact, the greater the production of renal 6-keto-PGF1 alpha was, the less the reduction of renal blood flow and urinary sodium excretion was. In the hypertensive subjects, however, these normal responses of the renal eicosanoid system, seen in the normotensives, were abolished; urinary 6-keto-PGF1 alpha was unaltered and thromboxane generation was rather increased. Thus, the renal eicosanoid system dysfunctions in hypertensive subjects when the renal circulation is challenged by norepinephrine. These abnormal responses are likely to cause sodium retention and could contribute, in part, to the hypertensive mechanism in patients with essential hypertension.     

Plasma epinephrine levels in hypertension and across gender and ethnicity

Epinephrine (E) infusions raise blood pressure and there is an excess incidence of hypertension among males and blacks. However, reports of E levels by ethnicity, gender, and blood pressure status are inconsistent. Insensitive assays, variability in plasma E levels within individuals, and the small size of most studies have contributed to these conflicting reports. We measured plasma E levels in a large diverse sample of subjects, using a highly sensitive assay. A total of 361 individuals participated in the study: 61% were men and 39% women, 74% were normotensive and 26% hypertensive, 59% were white and 41% were black. Except for difference in blood pressure and body mass index between the normotensives and hypertensives, subjects had similar baseline characteristics and took no antihypertensive medications for at least five days prior to sampling. All blood samples were collected after resting for a least 30 minutes following the insertion of an indwelling i.v. catheter. Catecholamine levels were determined using a radioenzymatic assay (assay sensitivities for E and norepinephrine were 6 pg/ml and 10 pg/ml, respectively). An ethnicity by gender interaction was found (F(1,315) = 5.126, p = .024). Subsequent analysis revealed that white women had significantly lower basal plasma E levels than white men (p <0.001) and black women (p = 0.036). There were no significant differences in E levels between black men and women or between white men and black men. Uncorrected E levels were lower in normotensive than hypertensive subjects (p = .009) but this difference was not significant when corrected for body mass index (BMI). Uncorrected norepinephrine levels were higher in women than men (p = .03) but the difference was no longer significant when corrected for BMI. Plasma E levels were significantly lower among white women than men or black women. In contrast to prior studies, E levels were lower in hypertensives, but this may reflect obesity among hypertensives.     

Plasma tumor necrosis factor-alpha levels and insulin resistance in nondiabetic hypertensive subjects

OBJECTIVES: Tumor necrosis factor-alpha (TNF-alpha) is associated with insulin resistance in certain conditions. However, whether TNF-alpha is related to insulin resistance in hypertensive subjects is still controversial. The aim of this study was to determine the status of TNF-alpha and insulin resistance in hypertension. METHODS: Newly diagnosed nondiabetic 17 essentially hypertensive (6 men, 11 women) patients, and 11 control healthy subjects (5 men, 6 women) are involved in the study. Body mass index (BMI), insulin, fasting blood glucose, cholesterol, triglyceride, and TNF-alpha levels were measured. Insulin resistance is assessed according to homeostasis model of assessment (HOMA-IR). RESULTS: Serum insulin (8.4 +/- 2.7 vs. 6.1 +/- 1.4 mIU/ml; p < 0.01), triglyceride (245.0 +/- 39.9 vs. 193.0 +/- 22.8 mg/dl; p < 0.01), and TNF-alpha (4.2 +/- 0.7 vs. 3.0 +/- 0.6 pg/ml; p < 0.001) levels, and HOMA-IR (2.0 +/- 0.8 vs. 1.3 +/- 0.3; p < 0.001) were significantly higher in the hypertensive patients compared to the normotensive control group. There were positive correlations between TNF-alpha levels and body mass index (r = 0.64, p < 0.01), and triglyceride (r = 0.55 p = 0.02) levels in the whole study group. However, there was no correlation of either TNF-alpha or HOMA-IR. CONCLUSIONS: Our data revealed that hypertensive patients have insulin resistance and higher TNF-alpha levels, but there is no relation between TNF-alpha levels and insulin resistance.     

Changes in metalloproteinases in healthy normotensive patients with high-normal blood pressure

INTRODUCTION: High-normal blood pressure (HNBP) seems to be related to increased cardiovascular risk in healthy, normotensive subjects, while essential hypertension is associated with an increase in extracellular matrix content, especially fibrillar collagen type I. The aim of our study was to investigate whether collagen degradation is altered in healthy normotensives with HNBP, and whether this alteration could be related to disturbances in the matrix metalloproteinases plasma concentration, and to compare the findings to those of healthy normotensives with normal blood pressure (NBP) levels, matched for age, sex and BMI. METHODS: Twenty six (14 males, 12 females) healthy, normotensive patients with HNBP, mean age 52 +/- 5 yrs, and BMI 23 +/- 1.5 kg/m(2) (group A), and 24, healthy normotensive patients (13 males, 11 females) with NBP, mean age 53 +/- 6 yrs, and BMI 23.2 +/- 1.4 kg/m(2) (group B), were studied. The two groups were matched for age, sex and BMI. Plasma levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitors (TIMP-1) and (TIMP-4) were determined by relevant ELISA in the study population. RESULTS: Plasma MMP-9 levels were significantly higher, while TIMP-1 and TIMP-4 levels were significantly lower in group A compared to group B, (MMP-9 579 +/- 147 versus 294 +/- 111 ng/mL, TIMP-1 178 +/- 45 versus 237 +/- 35 ng/mL p < 0.01, and TIMP-4 2.2 +/- 1.4 versus 4.4 +/- 2.1 p < 0.04 respectively). CONCLUSIONS: Our findings suggest that healthy normotensives with high-normal blood pressure have significantly increased MMP-9 and decreased TIMP-1 and TIMP-4 plasma levels compared to healthy normotensives with normal blood pressure. These findings need further investigation.     

Insulin resistance, oxidative stress, hypertension, and leukocyte telomere length in men from the Framingham Heart Study

Insulin resistance and oxidative stress are associated with accelerated telomere attrition in leukocytes. Both are also implicated in the biology of aging and in aging-related disorders, including hypertension. We explored the relations of leukocyte telomere length, expressed by terminal restriction fragment (TRF) length, with insulin resistance, oxidative stress and hypertension. We measured leukocyte TRF length in 327 Caucasian men with a mean age of 62.2 years (range 40-89 years) from the Offspring cohort of the Framingham Heart Study. TRF length was inversely correlated with age (r = -0.41, P < 0.0001) and age-adjusted TRF length was inversely correlated with the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (r =-0.16, P = 0.007) and urinary 8-epi-PGF(2alpha) (r = -0.16, P = 0.005) - an index of systemic oxidative stress. Compared with their normotensive peers, hypertensive subjects exhibited shorter age-adjusted TRF length (hypertensives = 5.93 +/- 0.042 kb, normotensives = 6.07 +/- 0.040 kb, P = 0.025). Collectively, these observations suggest that hypertension, increased insulin resistance and oxidative stress are associated with shorter leukocyte telomere length and that shorter leukocyte telomere length in hypertensives is largely due to insulin resistance.     

Insulin impairs endothelium-dependent vasodilation independent of insulin sensitivity or lipid profile

Insulin resistance is a risk factor for atherosclerosis and is associated with hyperinsulinemia, abnormal lipid profile, and hypertension. Whether hyperinsulinemia affects vascular function independent of insulin resistance or other metabolic risk factors is unknown. This investigation aimed to assess the effects of hyperinsulinemia on endothelial function in subjects with a spectrum of insulin sensitivity and lipid profile. Endothelium-dependent (flow-mediated dilation, FMD) and -independent (nitroglycerin) responses of the brachial artery were studied by high-resolution ultrasound before and during hyperinsulinemia (euglycemic clamp) in 25 normoglycemic, normotensive subjects. Participants were divided into an insulin-sensitive and an insulin-resistant subgroup based on their sensitivity index values, with a cutoff of 8, and into a normal-cholesterol and a high-cholesterol subgroup based on their total cholesterol levels, with a cutoff of 5.2 mmol/l (200 mg/dl). In the whole population, FMD was lower during hyperinsulinemia compared with baseline (2.3 +/- 0.6% vs. 6 +/- 0.6%; P < 0.001). Resting FMD was lower in the insulin-resistant subgroup compared with the insulin-sensitive subgroup (4.2 +/- 0.9% vs. 7.4 +/- 0.8%; P = 0.014) and in the high-cholesterol subjects compared with the normal-cholesterol subjects (4.4 +/- 0.7% vs. 8 +/- 0.7%; P = 0.002). Hyperinsulinemia decreased FMD in both the insulin-sensitive (from 7.4 +/- 0.8% to 3.6 +/- 0.4%; P < 0.001) and insulin-resistant (from 4.2% to 1.22%; P = 0.012) subgroups and in both the normal-cholesterol (from 8 +/- 0.7% to 3.9 +/- 0.4%; P < 0.001) and high-cholesterol (from 4.4 +/- 0.7% to 1.1 +/- 0.8%; P = 0.01) participants. Acute hyperinsulinemia impairs conduit vessel endothelial function independent of insulin sensitivity and lipid profile. Insulin may trigger endothelial dysfunction and promote atherosclerosis.     

Influence of age, body mass index, and blood pressure on the carotid intima-media thickness in normotensive and hypertensive patients.

We investigated whether body mass index and blood pressure have an additive influence on the carotid intima-media thickness (IMT). In 27 patients treated for hypertension (47.2+/-8.7 years) and 23 normotensive subjects (44.1+/-8.1 years), 24-h recording of blood pressure was performed. The carotid IMT was determined by ultrasonography and baroreflex sensitivity by a spectral method from 5-min recordings of blood pressure. Significant differences between hypertensive and normotensive subjects were observed for carotid IMT (0.60+/-0.08 vs. 0.51+/-0.07 mm; p<0.001) and baroreflex sensitivity (3.5+/-1.8 vs. 5.6+/-2.1 ms/mm Hg; p<0.001). Hierarchical multiple regression analysis (p<0.01) showed that carotid IMT was positively correlated with age (p<0.001) and body mass index (p<0.05) in normotensive subjects. The increased carotid IMT in hypertensive patients was not additively influenced by either age or body mass index. Baroreflex sensitivity decreased with age (p<0.01) and with carotid IMT (p<0.05) in normotensive subjects only. Multiregression analysis showed that an additive influence of age and body mass index on the development of carotid IMT is essential only in normotensive subjects. In hypertensive subjects the influence of blood pressure predominates, as documented by a comparison of the carotid IMT between hypertensive and normotensive subjects.     

Habituation of the cold pressor response in normo- and hypertensive human subjects

The changes in cardiovascular response to repeated cold-pressor test were studied in young normotensive and in young hypertensive subjects. The cold stimulus consisted of immersing one foot in cold water (4 degrees C) for 60 s. Non-invasive methods were used to record the cardiovascular responses: blood flow of the calf was measured using venous occlusion plethysmography, arterial blood pressure with sphygmomanometery, heart rate with electrocardiography. The vascular conductance level in the calf was higher in hypertensive subjects than in normotensives. The difference remained throughout the series of 6 daily experiments. In both hypertensive and normotensive groups of subjects some individuals responded to the cold stimulus with vasodilatation in the calf muscles, others with vasoconstriction. In the hypertensives blood flow increased more and habituation was only transient with a strong tendency for the vasodilatory response to recover, while in normotensives habituation was rapid and complete. Vasoconstrictor responses showed no signs of reduction. The blood pressure increases were larger in hypertensives and remained unaltered within the period of repeated tests (6 days). There was not significant difference between the heart rate changes in the two groups of subjects. It is concluded that the vasculature of the calf shows lower tone and is more labile during the early stage of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)     

Second derivative of the finger arterial pressure waveform: an insight into dynamics of the peripheral arterial pressure pulse

The study investigated second derivative of the finger arterial pressure waveform (SDFAP) in 120 healthy middle-aged subjects and in 24 subjects with essential hypertension. SDFAP consists of 5 sequential waves 'a'-'e'. Their normalized magnitudes (B/A, C/A, D/A, and E/A) were calculated. In multivariate regression analysis, B/A and C/A correlated only with age. D/A independently correlated with age, heart period, mean blood pressure (MBP), body height, and gender. E/A independently correlated with age and MBP. D/A and E/A were higher (0.42+/-0.16 vs. 0.33+/-0.14, p = 0.05 and 0.63+/-0.15 vs. 0.45+/-0.14, p < 0.001), while B/A and C/A were lower (1.04+/-0.16 vs. 1.20+/-0.17, p = 0.002 and 0.09+/-0.15 vs. 0.26+/-0.20, p = 0.001) in hypertensives compared to sex- and age-matched controls. After the adjustment for MBP, heart period, and body mass index (ANCOVA), independent discriminative power was preserved only for indices B/A and C/A (p = 0.001 and 0.021, respectively). Therefore, B/A and C/A provide additional information about simple clinical characteristics and might reflect the structural alteration of the arterial wall in hypertensive subjects.     

Kidney stones and hypertension: population based study of an independent clinical association.

OBJECTIVE--To test the hypothesis that kidney stone disease is more frequent among hypertensive men when the effect of possible confounders is allowed for. DESIGN--Cross sectional study of a sample of the male working population conducted as part of the 10 year follow up of a nationwide survey of the prevalence of cardiovascular risk factors. SETTING--The Olivetti factory in Pozzuoli, a suburban area of Naples. POPULATION--688 Male workers (87.9% of the male workforce) aged 21-68. INTERVENTIONS--Anthropometric and blood pressure measurements, blood tests, and administration of a detailed questionnaire aimed at detecting a history of urolithiasis. MAIN OUTCOME MEASURES--Prevalence of a history of urolithiasis among normotensive and untreated and treated hypertensive men adjusted for the possible confounding effects of age, body mass index, renal function, and serum urate and total calcium concentrations. RESULTS--Of the 688 participants 509 were normotensive. Of the remainder, 118 had untreated and 61 treated hypertension. The overall prevalence of a history of urolithiasis was 16.3% (112/688). The relative risk of hypertensive subjects having a history of kidney stones was twice that of the normotensive group (odds ratio 2.11; 95% confidence interval 1.17 to 3.81), the risk being higher when only treated hypertensives were considered (odds ratio 3.16; 95% confidence interval 1.75 to 5.71). The prevalence of a history of urolithiasis was 13.4% (68/509) in the normotensive subjects, 20.3% (24/118) in the untreated hypertensives, and 32.8% (20/61) in the treated hypertensives (p less than 0.001). The age adjusted relative risk in treated hypertensive men was higher than that in the normotensive group (Mantel-Haenszel pooled estimate of odds ratio 2.63; 95% confidence interval 2.23 to 3.10). CONCLUSION--An independent clinical association exists between the occurrence of urolithiasis and hypertension. The increased urinary calcium excretion commonly detected in hypertension may be the pathogenetic link.     

Evaluation of intra-erythrocyte Na+ activity in persons at high risk for essential arterial hypertension and as an aid in differential diagnosis from secondary forms of hypertension

The intracellular "Na+ activity" was measured in erythrocytes of normotensive subjects (46), in essential hypertensive patients (18), in their children (20) and in patients with secondary hypertension (8). In normotensive subjects without a genetic trait of hypertension intracellular "Na+ activity" was 7.3 +/- 0.8 mmol/l, in secondary hypertensive patients was 7.5 +/- 0.6 mmol/l, in essential hypertensive patients was 10.9 +/- 1.1 mmol/l and in their children was 8.6 +/- 2.1 mmol/l. In this group (children) it was possible to differentiate between 2 population, the 1 degree with height intracellular "Na+ activity" (8); the 2 degrees with normal intracellular "Na+ activity".     

23Na NMR evaluation of human erythrocytes Na+/K+/CL-cotransport. A study in elderly hypertensives.

The behaviour of sodium transport systems across the cell membrane has been poorly investigated in elderly hypertension. Sodium efflux driven by Na+/K+/Cl-cotransport activity was therefore investigated (using a novel NMR-spectroscopy method) in 5 elderly hypertensive males (mean age 78 +/- 5 years) and 5 normotensive controls (mean age 79 +/- 3 years). In order to exclude any change in cotransport activity secondary to metabolic abnormalities, both patients and controls were non-obese and had normal glucose and lipid metabolisms. The Na+/K+/Cl-cotransport evaluation was performed after three months of pharmacological wash-out, under a diet containing 120 mEq of Na+/day. The resulting data showed that Na+ efflux due to outward Na+/K+/Cl-cotransport was higher in hypertensive group than in the normotensive one (0.50 +/- 0.10 mmol Na+/l cells/hr. vs 0.33 +/- 0.03 mmol Na+/l cells/hr., respectively, p < 0.05). Intracellular Na+ content was similar in both groups. At variance with previous data from the literature, our findings indicate that the Na+/K+/Cl-cotransport activity is elevated in elderly hypertensives.     

Acute angiotensin II increases plasma F2-isoprostanes in salt-replete human hypertensives

Angiotensin (Ang) II induces oxidative stress in vitro and in animal models of hypertension. We tested the hypothesis that Ang II increases oxidative stress in human hypertension, as assessed by plasma F2-isoprostane concentrations. Plasma F2-isoprostanes, hemodynamic and endocrine parameters were measured at baseline and following a 55 min infusion of 3 ng/kg/min Ang II in 13 normotensive and 13 hypertensive volunteers ingesting a high- (200 mmol/d) or low- (10 mmol/d) sodium diet. Mean arterial pressure (MAP) and body mass index were higher in hypertensive subjects. Ang II infusion increased MAP (p<.001) and plasma aldosterone concentrations (p<.001) and decreased plasma renin activity (p<.001) and renal plasma flow (p<.001) to a similar extent in both groups. Plasma F2-isoprostane concentrations were similar at baseline. There was no effect of Ang II on F2-isoprostane concentrations during low-salt intake in either group (normotensive 51.7 +/- 7.1 to 53.7 +/- 6.5 pg/ml and hypertensive 52.2 +/- 8.2 to 56.2 +/- 10.0 pg/ml; mean +/- SE). During high-salt intake, Ang II increased F2-isoprostane concentrations in the hypertensive group (52.3 +/- 7.2 to 63.2 +/- 10.4 pg/ml, p=0.010) but not in the normotensive group (54.2 +/- 4.4 to 58.9 +/- 6.6 pg/ml, p=0.83). Acute Ang II infusion increases oxidative stress in vivo in hypertensive humans. The renin-angiotensin system may contribute to oxidative stress in human cardiovascular disease.     

Plasma leptin levels strongly correlate with plasma renin activity in patients with essential hypertension.

Previous studies demonstrated elevated plasma leptin and angiotensinogen (PRA) levels in essential hypertension. However, a few studies investigated the relationship between leptin and angiotensinogen levels in both lean and overweight/ obese hypertensives. The aim of the present study was therefore to examine the relationship between blood pressure, leptin and plasma renin activity in normotensives and in both lean and overweight/obese patients with essential hypertension. Two groups of subjects who were carefully matched for age, gender, waist:hip ratio and body mass index (BMI) were studied: 28 normotensives (NT) (age: 40.1+/-9.1 years old, BMI: 28.1+/-3.6 kg/m2, male/female: 18/10) and 33 newly diagnosed mild to moderate essential hypertensives (EHT) (age: 38.9+/-10 years old, BMI: 27.9+/-4.8 kg/m2, male/female: 22/11). No significant differences in age, gender, waist:hip ratio, fasting blood glucose and BMI were detected between EHT and NT groups. However, systolic and diastolic pressures, mean arterial blood pressures, plasma leptin levels and PRA were significantly higher in EHT group than in NT group (P = 0.001). Plasma leptin levels were strongly correlated with BMI in EHT (r=0.67, P = 0.001) and NT groups (r=0.44, P = 0.001). Plasma leptin levels were correlated with plasma PRA levels in both EHT and NT groups (r = 0.66 and r = 0.44; both P < 0.05, respectively). There was no correlation between leptin or PRA and systolic, diastolic pressures, or mean arterial blood pressures. Furthermore, the patients were divided as lean (n=16) and overweight/obese (n = 17) and compared with BMI-matched controls. In both subgroups, plasma leptin and PRA levels were also higher than those of controls. Our results showed that elevated plasma leptin and PRA are associated with hypertension in both lean and overweight/obese hypertensives. Moreover, plasma leptin was significantly correlated with plasma angiotensinogen levels. These findings suggest that adipose mass is an important determinant of blood pressure, although the mechanism is not clear.     

Perception of arterial hypertension and myocardial infarction in hypertensive and normotensive men and women

The research aims were to test perception of arterial hypertension and myocardial infarction in hypertensive and normotensive men and women as well as to test perception of arterial hypertension and myocardial infarction as predictors of blood pressure control in hypertensives. In the research 470 subjects of 4 general practices from Rijeka, Croatia participated, hypertensive group from the list of hypertensive patients without cardiovascular complications and other major chronic conditions, normotensive group from the list of patients without chronic conditions. Each group had 235 subjects, 128 men and 107 women. Perception of hypertension and myocardial infarction was measured as the result on semantic differential questionnaire. Factor analysis extracted evaluation, potency and activity factor. Blood pressure control was interpreteted on the five degrees scale. Statistical significance was defined under 5% (p < 0.05). Hypertensive subjects perceived hypertension as less negative and more active, while myocardial infarction was perceived as more potent term than by normotensives. Women perceived myocardial infarction as less negative, and less potent term than men. Both groups perceived myocardial infarction as more negative, potent and active term than hypertension. Normotensive women evaluated hypertension as more negative, and perceived myocardial infarction as less potent than other subjects. Well-controlled hypertension was correlated with a lower potency of hypertension and lower activity of myocardial infarction. Both conditions are perceived as more "male" diseases. As perception of hypertension and myocardial infarction is correlated with blood pressure regulation in hypertensives, and hypertension is major risk factor for myocardial infarction, family doctors should put additional effort in changing perception of cardiovascular diseases in their patients, especially in women.