Stages Of Essential Hypertension Research Articles

Renal Surrogates in Essential Hypertension

The kidney can be considered both as culprit and victim in the hypertensive process. Renal functional derangement contributes to the development of arterial hypertension and the development of secondary vascular damage both at the glomerular and arteriolar level accounts for the development of progressive nephrosclerosis. The most common alteration of renal function observed in humans since the early stages of essential hypertension is the presence of renal vasoconstriction. This can be accompanied by the appearance of hyperuricemia, increased urinary excretion of enzymes such as N-acetyl-beta-glucosaminidase and of proteins like albumin and beta2-microglobulin. Later on, a progressive fall in glomerular filtration rate accompanied or not by proteinuria can be observed if high blood pressure persists.

Haemodynamics in hypertension

The haemodynamic changes that occur during the development of established essential hypertension can be detected only by longitudinal studies. Several long-term studies thus indicate that the circulation in essential hypertension shifts from a ‘high-output, normal resistance' state in young age toward a ‘low-output, high-resistance’ state in old age. However, this pattern is not a uniform one, and essential hypertension may also start by an increase in peripheral resistance without a prior phase of an elevated cardiac output. The reasons for these different haemodynamic patterns are not yet understood. Sympathetic overactivity may, at least in part, be responsible for the haemodynamic changes seen in the starting phase of essential hypertension. The haemodynamic characteristics in the different developmental stages of essential hypertension may vary considerably and are also influenced by ageing. Therefore, the proper use of anti-hypertensive drug treatment should be directed individually according to the underlying haemodynamic disturbances.

Empiric determination of the transition from concentric hypertrophy to congestive heart failure in essential hypertension

Our aim was to determine whether there is a final transition from left ventricular hypertrophy to congestive heart failure in the late stage of essential hypertension. A theoretic model using the concept of systolic transmural nonuniform wall thickening was applied to develop a concentric two-shell geometry allowing evaluation of the mechanics of circumferential midwall fibers. We evaluated pressure-volume data from 46 normal control subjects (control group) and 70 patients with hypertension: 33 without hypertrophy (hypertension only group), 14 with hypertrophy (hypertrophy group) and 23 with heart failure in addition to hypertrophy (heart failure group). End-diastolic volume index was higher in the heart failure group than in the control group (p < 0.01). Although left ventricular wall thickness and mass index were increased in both the hypertrophy and the heart failure group, concentricity indexes as assessed by ratios of left ventricular wall thickness to dimension and mass index to end-diastolic volume index were maximal in the former. Although endocardial and standard midwall fractional shortening did not differ among the control, hypertension only and heart failure groups, that of the modified midwall by concentric two-shell geometry was decreased in the hypertrophy and the heart failure groups (p < 0.05). The Hotelling T2 test and Mahalanobis distance clearly discriminated the latter two groups with end-systolic stress and modified midwall fractional shortening relation. A fitting segmented regression model predicted a progression to hypertrophy and identified a transition from hypertrophy to heart failure by a combination of modified midwall fractional shortening and concentricity indexes.

Renal Damage in Hypertension

The kidney can be considered as both culprit and victim in the hypertensive process. Deranged renal function contributes to the development of arterial hypertension and of secondary vascular damage at the glomerular and arteriolar level and accounts for the development of progressive nephrosclerosis. The most common alteration of renal function observed in humans from the early stages of essential hypertension is the presence of renal vasoconstriction. This can be accompanied by hyperuricaemia and increased urinary excretion of enzymes such as N-acetyl-beta-glucosaminidase and proteins such as albumin and beta 2-microglobulin. Later, a progressive fall in glomerular filtration rate, sometimes accompanied by proteinuria, can be observed if high blood pressure persists.

Haemostatic variables in arterial hypertension.

In 22 untreated patients with uncomplicated essential hypertension and in 10 normotensive subjects the plasma levels of thrombomodulin (TM), beta-thromboglobulin (beta-TG), D-dimer (DD), tissue-type plasminogen activator (t-PA) and plasminogen activator-inhibitor (PAI-1) were evaluated. The observed values show no significant difference in plasma TM, plasma and urine beta-TG concentration and plasma DD among hypertensive patients and controls. On the other hand, the levels of t-PA and PAI-1 in hypertensive patients were significantly higher than the values detected in normotensive control subjects. These data seem to indicate that, at initial stages of essential hypertension, the t-PA and PAI-1 levels increase.

Diagnostic significance of dopamine estimation using plasma and urine in patients with adrenal and renal insufficiency, renal transplantation and hypertension.

Although free and conjugated dopamine (DA) constitute most of the plasma and urine catecholamine pool, the diagnostic significance of DA estimation for the evaluation of illness is not clear. We evaluated the clinical utility of DA estimation by measuring free and conjugated DA in patients with various illness. Patients with adrenal insufficiency did not show decreases in DA concentrations but did demonstrate reductions in free and conjugated plasma adrenaline (Ad). Patients with established stage of essential hypertension exhibited decreased plasma concentrations of free and conjugated DA, although they were hyperadrenergic. In patients with chronic renal insufficiency and failure, the free DA concentration in the urine decreased depending on the severity of renal impairment. Conversely, plasma concentrations of conjugated DA are higher in patients with chronic renal failure than in normal subjects. The high plasma concentrations of conjugated DA decreased dramatically following hemodialysis and renal transplantation. Urinary free DA excretion increased markedly following renal transplantation. In conclusion, the estimation of the free and conjugated DA in plasma and urine is clinically useful for the diagnosis of adrenal insufficiency, essential hypertension, and renal insufficiency and failure. It also can be used to monitor the effectiveness of hemodialysis and renal transplantation.

Genetic influences on plasma catecholamines in human twins.

We examined the relative genetic and environmental influences on the variability in plasma epinephrine, norepinephrine, and dopamine levels in 109 twin pairs. Epinephrine levels were lower in females (P = 0.048). The norepinephrine concentration increased with age (r = 0.40; P < 0.001). Blood pressure (BP) was not associated with epinephrine levels in either sex or with norepinephrine levels in females. In males, there was a positive association between norepinephrine concentration and diastolic BP (r = 0.31; P = 0.020). A negative association between dopamine levels and systolic and diastolic BP in females (r = -0.22; P = 0.014 and r = -0.20; P = 0.027, respectively) was not maintained after accounting for age, body mass index, and sex. Using path analysis and maximum likelihood model fitting, genetic, unique environment, and age effects contributed 57% (P < or = 0.001), 27% (P < or = 0.001), and 16% (P < or = 0.001) to the variability in norepinephrine, respectively. Genetic effects explained 64% (P < 0.1) and 74% (P < 0.1) of the variability in epinephrine concentrations in females and males, respectively. Unique environmental influences explained the remainder. Genetic and unique environmental effects explained 72% (P < 0.01) and 28% (P < or = 0.001) of the variability in dopamine levels. These results indicate a substantial genetic influence on plasma catecholamine levels. Although consistent associations between plasma catecholamines and BP were not evident in this study, the observed genetic influence on circulating catecholamines may be relevant to the potential role of the sympathetic nervous system in the early stages of essential hypertension.

Evaluation of Cardiac Function with Radionuclide Angiography in Hypertension

Alterations of left ventricular systolic and diastolic function at rest and during exercise have been described in the first stages of coronary artery disease, hypertrophic cardiomyopathy and essential hypertension. Ab~ormalities in the systolic response to exercise are common in patients with hypertension, and can be caused by diastolic changes that have been reported as very early indications of this disease. Widespread prescribing of ,,-blockers for the treatment of hypertension must take into account that these drugs usually depress cardiac function and therefore aggravate the systolic performance, which is already impaired. For this reason, a new class of ,,-blockers (hybrid drugs with vasodilator properties) that may be devoid of these effects is now under intensive investigation. One of these novel drugs, nebivolol, was used to assess modifications of the cardiac performance in patients with hypertension, using radionuclide angiography (RNA).

Suppressed dopaminergic activity and water‐sodium handling in the kidneys at the prehypertensive stage of essential hypertension

1. In this study, the question of whether the suppression of the renal dopaminergic system is primary or not was investigated. 2. Renal dopaminergic activity was compared between young healthy normotensive subjects without a family history of hypertension (FH(-] and those with a family history of hypertension (FH(+]. 3. A significant decrease in urinary free dopamine excretion was noted, and the responses of urine volume, urinary sodium excretion, and fractional excretion of sodium to infused dopamine were significantly augmented in FH(+). In addition, a normal level of l-dopa delivery at the renal proximal tubules and a significant reduction in the conversion of l-dopa to dopamine in the kidney were found in FH(+). 4. These findings suggest that renal dopaminergic activity is already suppressed at the prehypertensive stage, and that the reduction in the conversion of l-dopa to dopamine in the proximal tubules may contribute to the attenuation of renal dopaminergic activity in FH(+).

Platelet calcium and quenched-flow aggregation kinetics in essential hypertension.

Abnormal platelet function may contribute to the complications of essential hypertension. We have studied the kinetics of platelet aggregation induced by adenosine diphosphate (ADP) or epinephrine, plasma beta-thromboglobulin, and basal, cytosolic, and free calcium, as correlates of platelet function. Fifteen untreated patients with essential hypertension and without detectable atherosclerosis, 18-40 years old, were compared with 30 matched normotensive control subjects. Maximal rates of platelet aggregation (Vmax) with ADP and epinephrine were significantly higher in patients than in control subjects (p less than 0.03), as assessed by quenched-flow aggregometry. However, significance was lost when Vmax was corrected for the platelet count. Paradoxically, the activation constants (Ka) for ADP were higher in patients than in control subjects (p less than 0.03). With ADP as the inducing agent, onset time (t) or lag period before aggregation begins was longer in patients than in control subjects (p less than 0.02). beta-thromboglobulin levels, an index of in vivo platelet activation, were not significantly different between the two groups (p = 0.13). The mean platelet cytosolic free calcium concentration was higher in patients (213 +/- 19 nM) than in control subjects (172 +/- 14 nM), but this difference was not statistically significant (p = 0.07). However, there was a close correlation between the free calcium level and systolic, diastolic, and mean blood pressure (p less than 0.003, p less than 0.04, p less than 0.004, respectively). No difference in platelet volume between the two groups was found. Our data suggest that platelets in the early stages of essential hypertension display an overall increased aggregation potential but a diminished sensitivity to ADP.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial natriuretic peptide (ANP) in relation to blood pressure: a study in middle‐aged men with normal and elevated blood pressure

In order to investigate the potential role of atrial natriuretic peptide (ANP) in mild to moderate essential hypertension, a study was conducted in groups of normotensive and hypertensive middle-aged men born in 1926 and 1927. Venous plasma concentrations of immunoreactive ANP (irANP) were studied in relation to measurements of cardiac structure and function, urinary electrolytes as well as some cardiovascular hormones. Plasma irANP did not differ between normotensive controls (31 +/- 14 pmol l-1) and borderline or untreated hypertensive patients. However, irANP concentrations were slightly but significantly (P less than 0.05) lower in the borderline (26 +/- 8 pmol l-1) compared to the untreated established hypertensives (35 +/- 14 pmol l-1). No relationships were found between irANP and blood pressure, indices of left ventricular structure and function or hormone parameters in subgroups or the whole study group. Our data do not support the view that plasma irANP is increased in uncomplicated essential hypertension, since our groups of borderline or established hypertensive middle-aged men without major cardiac involvement did not differ in irANP concentrations compared to normotensive controls. Thus, during the development or in the early stages of essential hypertension, ANP secretion does not seem to be abnormal.

Function of Myocardial Contraction and Relaxation in Essential Hypertension in Dynamics of Acupuncture Therapy

Forty-nine patients with initial stages of essential hypertension (EH) were investigated using phase systole analysis and echocardiography during acupuncture (reflexotherapy) treatment. It was established that even at the initial stages of EH increasing of myocardial mass and the disturbances of contractile and diastolic activity of myocardium take place. As a result of acupuncture a stable hypotensive effect, improvement or normalization of contractile function and diastolic values, a decrease of energy loss, reversal of myocardial hypertrophy were achieved. It is the decrease of sympathetic influences on the circulation system that plays an important part in the onset of these positive changes.

Plasma beta-thromboglobulin to platelet factor 4 ratios as indices of vascular complications in essential hypertension

The ratio of the plasma level of beta-thromboglobulin (beta-TG) to platelet factor 4 (PF-4) which is regarded as a most reliable indicator of platelet activation in vivo, was followed in 52 subjects at various stages of essential hypertension according to the WHO classification. These comprised 30 cases at stage I, 19 cases at stage II and three cases at stage III, and 20 age-matched normotensive control subjects. The observed beta-TG:PF-4 ratio in the hypertensive patients was 4.59 +/- 0.20, which was significantly higher than the value of 3.13 +/- 0.19 recorded in the normotensive control subjects. According to the WHO classification, beta-TG:PF-4 ratios in hypertensive patients at stages I, II and III were 3.93 +/- 0.19, 5.31 +/- 0.35 and 6.56 +/- 0.12, respectively. The beta-TG:PF-4 ratio revealed a tendency of platelet activation to increase with advanced progress of hypertensive vascular lesions. These results suggest that the abnormal platelet function observed in patients with essential hypertension plays an important role in the development of hypertensive vascular complications.

Circulating Inhibitors of Sodium Transport at the Prehypertensive Stage of Essential Hypertension

Alterations in cellular calcium metabolism are presumed to be the basis of the vasoconstrictive process that sustains elevations in arterial pressure. Altered membrane sodium transport can effect changes in intracellular free calcium concentration through changes in transmembrane sodium gradients and membrane depolarization. Thus, changes in membrane sodium transport could produce calcium accumulation in vascular smooth muscle, resulting in vasoconstriction and arterial hypertension. Multiple sodium transport abnormalities exist in tissues of genetically hypertensive rats, and blood cells of human essential hypertensives. Na+-K+ cotransport and Na+-Li+ countertransport abnormalities appear to be primary membrane defects, but a direct physiologic link of these to vasoconstriction remains to be established. Evidence for circulating Na,K-ATPase inhibitors in hypertension is now widely reported, and Na,K-ATPase inhibition provides a rationale for vasoconstriction through altered calcium and/or neurotransmitter metabolism. Na,K-ATPase inhibition in hypertensive disease appears to arise not as a primary abnormality in membrane transport, nor as a phenomenon secondary to hypertension per se, but as a physiological response to compensate for excess extracellular fluid volume accumulation.

Circulating Inhibitors of Sodium Transport at the Prehypertensive Stage of Essential Hypertension

Circulating Inhibitors of Sodium Transport at the Prehypertensive Stage of Essential Hypertension

Renal Abnormalities at the Prehypertensive Stage of Essential Hypertension

An approach to evaluating the genetic components of essential hypertension using an animal model, the Milan hypertensive strain (MHS) of rats, and studies in human families with positive and negative histories for high blood pressure are described and discussed. Differences at renal and cellular levels between MHS and its normotensive control strain, MNS, show many similarities to those between offspring from hyper- and normotensive families in humans. These include, with respect to the former group of each species, lower erythrocyte volume and Na content, higher Na-K cotransport across red blood cell (RBC) membranes higher Na excretion after load, and greater pressor effect in transplanted kidneys. A novel protein found in rat RBC cytoskeleton appears to have a function in Na-K cotransport and it may, eventually, be possible to demonstrate in man.

Renal Abnormalities at the Prehypertensive Stage of Essential Hypertension

Summary: An approach to evaluating the genetic components of essential hypertension using an animal model, the Milan hypertensive strain (MHS) of rats, and studies in human families with positive and negative histories for high blood pressure are described and discussed. Differences at renal and cellular levels between MHS and its normotensive control strain. MNS, show mane similarities to those between offspring from hyper- and normotensive families in humans. These include. with respect to the former group of each species. lower erythrocyte volume and Na content, higher Na-K cotransport across red blood cell (RBC) membranes higher Na excretion after load, and greater pressor effect in transplanted kidneys. A novel protein found in rat RRC cytoskeleton appears to have a function in Na-K cotransport and it may. eventually. he possible to demonstrate in man.

Hemodynamic Consideration in Clinical Hypertension

Hypertension by definition is a hemodynamic disorder. The hemodynamic characteristics of the different stages of essential hypertension are discussed, with particular emphasis on the involvement of the heart and kidneys.

Enhanced red cell sodium permeability in patients with borderline hypertension.

Red cell membrane sodium permeability was studied in 41 untreated patients with essential hypertension (20 borderline hypertensives and 21 established hypertensives) and 21 age matched normotensive subjects by means of the measurement of unidirectional passive influx of 22Na+ into ouabain-treated erythrocytes. The mean value (+/- SD) of 22Na+ influx was greater in the hypertensives than in the normotensives (0.183 +/- 0.047 vs 0.152 +/- 0.047 mmol/l . cells/hr, respectively, p less than 0.02). Among the patients with essential hypertension, the borderline hypertensives demonstrated a higher 22Na+ influx than the established hypertensives (0.207 +/- 0.043 vs 0.160 +/- 0.038 mmol/l . cells/hr, respectively, p less than 0.001), and 22Na+ influx positively correlated with plasma renin activity (r = 0.44, p less than 0.005). In 16 of 20 borderline hypertensives, 5 year blood pressure changes were examined retrospectively, and a positive correlation was observed between mean blood pressure increase and 22Na+ influx value in these subjects (r = 0.64, p less than 0.01). These results suggest that passive sodium influx may be altered in the course of the development of hypertension in relation to the changes in blood pressure level and that enhanced sodium permeability may be a characteristic of the early stage of essential hypertension.

Plasma Concentrations of Platelet-Specific Proteins in Different Stages of Essential Hypertension: Interactions between Platelet Aggregation, Blood Lipids and Age

Plasma beta-thromboglobulin (beta TG) and platelet factor 4 (PF4) were significantly higher in a group of 116 hypertensive men than in a normotensive group of 142 men. They increased with the stage of hypertension but the level did not correlate with the age of the subjects. Platelet aggregation was similar in the two groups and positively correlated with the age of the subjects in the normotensive group but not in the hypertensive group. A strong positive correlation was observed between the levels of plasma beta TG and PF4 and between platelet aggregation to ADP and that to epinephrine in both the hypertensive and normotensive groups. However, there was no correlation between the level of plasma beta TG or PF4 and platelet aggregation. Plasma antithrombin III was lower in the hypertensive group than in the normotensive group. These studies suggest that plasma levels of beta TG and PF4 are closely related to the stage of hypertension and are better indicators than aggregation of in vivo platelet activation in hypertensive subjects. Enhanced platelet activation may be involved in the acceleration of hypertensive arteriovascular damage and atherosclerosis.