Pathogenesis Of Primary Hypertension Research Articles

Abnormal erythrocyte sodium leak in a subset of essential hypertensive patients

We measured the ouabain- and bumetanide-resistant Na+ efflux in Mg2+-sucrose medium (passive Na+ leak) in erythrocytes from 30 normotensive controls and 72 essential hypertensive patients. The mean values (+/- SEM) of the rate constant of Na+ leak (kpNa) were not significantly different between normotensives and hypertensives. Nevertheless, using the 95% confidence limits of the kpNa (in 10(-3).h-1) in the normotensive group as a cut-off point, 7 (9.7%) essential hypertensives exhibited increased values (58.96 +/- 10.12) when compared with the other 65 patients (23.86 +/- 0.74). revealing increased passive Na+ permeability in the former (leak "+" hypertensives). Na+ fluxes depending on the Na+-K+ pump, outward Na+-K+ cotransport, and Na+-Li+ countertransport were also measured in fresh erythrocytes from the same 72 patients. Three of them (4.2%) exhibited decreased values of ouabain-sensitive Na+ efflux and 6 (8.3%) of bumetanide-sensitive Na+ efflux, while 8 patients (11.1%) showed increased values of Li+-stimulated Na+ efflux and, finally, 48 patients (59.7%) did not present any evident abnormality in these Na+ transport systems. No differences were observed between leak "+" hypertensives and the remaining 65 patients when both basal erythrocyte Na+ content and clinical parameters of hypertension were compared. However, Na+ efflux depending on the outward Na+-K+ cotransport was significantly higher in the leak "+" hypertensive subset (299.43 +/- 43.18 vs 181.52 +/- 10.76 mumol.(l cells.h)-1; P = 0.0078), suggesting a compensatory phenomenon. Enhancement of Na+ permeability detected in 3% to 16% of essential hypertensives may be implicated in the pathogenesis of primary hypertension.

Influence of experimental hyperthyroidism on blood and myocardial serotonin in rats.

Recent reports suggest a role for serotonin in the pathogenesis of primary hypertension and left ventricular (LV) hypertrophy. In this study, we have induced LV hypertrophy by oral feeding of thyroxine at increasing dosages (150-450 micrograms/kg b.wt.) over a 5-week period. The effects of hyperthyroidism on cardiovascular parameters, blood and myocardial serotonin concentrations were assessed. Water-fed rats and formerly hyperthyroid recovered animals served as controls. Thyroxine caused a significant LV hypertrophy: hyperthyroid rats 2.19 +/- 0.16*; controls 1.65 +/- 0.13 g/kg b.wt. (mean +/- SD; *P less than 0.05). An almost complete regression of LV hypertrophy occurred in the recovery group (1.66 +/- 0.20 g/kg b.wt.) 3 weeks after cessation of thyroid hormone application. Thyroxine-treated animals showed a significant increase of serotonin blood levels (thyroxine rats: 2108 +/- 781*, recovery: 1132 +/- 726, controls: 705 +/- 480 ng/ml; *P less than 0.05). The concentrations of serotonin in left ventricular myocardium were increased after thyroid hormone application, whereas the highest levels were found in the recovery group (thyroxine rats: 139.1 +/- 30.4, recovery: 167.2 +/- 43.1, controls: 68.9 +/- 27.9 mg/ml homogenate). Serotonin-containing cells in the left ventricular myocardium were stained immunohistochemically. They were localized perivascularly and were assumed to represent tissue mast cells. In experimental hyperthyroidism the serotonin levels in blood and heart are increased possibly indicating an interaction of both hormones in thyroxine-induced cardiomyopathy.

Cellular calcium metabolism in primary hypertension

Several disturbances of cellular Ca2+ metabolism have been described in essential hypertension and in the spontaneously hypertensive rat. Possibly the elevation of intracellular free Ca2+ concentration in arterial smooth muscle cells is one important step in the pathogenesis of primary hypertension. In most studies a decreased energy-dependent Ca2+ transport has been proposed as a mechanism. However, disturbances in cellular Ca2+ metabolism, which can be exclusively ascribed to essential hypertension, have not yet been found. The cause of altered cellular Ca2+ transport in primary hypertension may either be a genetically determined defect of membrane transport or a still-unidentified humoral factor.

Calcium and Primary Hypertension

The role of dietary calcium in essential hypertension remains controversial. Various studies have found on the one hand a weak negative correlation between blood pressure and Ca2+ intake in special groups, and on the other hand a positive correlation between serum Ca2+ concentration and blood pressure. Several disturbances of cellular Ca2+ metabolism have been described in essential hypertension and in the spontaneously hypertensive rat. Possibly the elevation of intracellular free Ca2+ concentration in arterial smooth muscle cells is one important step in the pathogenesis of primary hypertension. In most studies a decreased energy-dependent Ca2+ transport has been proposed as a mechanism. However, disturbances in cellular Ca2+ metabolism, which can be exclusively ascribed to essential hypertension, have not yet been found. The cause of altered cellular Ca2+ transport in primary hypertension may either be a genetically determined defect of membrane transport or a still unidentified humoral factor.

Erythrocyte Na+-Li+ countertransport and blood viscosity in arterial hypertension.

The aim of this study was to evaluate together the main hemorheologic parameters and one of the transmembrane ion transport systems in erythrocytes of subjects with normal and elevated blood pressure. Three sex-, age-, and weight-matched groups consisting of 15 normotensive subjects (NT) with no parental hypertension, 15 patients with essential hypertension (EH) at stage 1-II WHO, and eight patients with secondary hypertension (Sec.H), respectively, were studied. Red blood cell Na+-Li+ countertransport (CTT), blood viscosity (eta B) at shear rates of 230 X S-1, 115 X S-1, and 46 S-1 and plasma viscosity (eta P) at shear rate of 46 X S-1 were measured. Plasma proteins and fibrinogen were also evaluated. CTT was higher in EH than in NT (P less than 0.01), while no significant difference was found between NT and Sec. H patients. eta B at 115 X S-1 and 46 X S-1 was higher in EH, but not in Sec. H, than in NT patients (P less than 0.05). No difference in eta P, plasma proteins and fibrinogen levels was observed between EH and NT. Elevated eta B and/or CTT may indicate a structural alteration in the erythrocyte membrane of some essential hypertensive patients. This is consistent with the hypothesis that a widespread membrane disorder is involved in the pathogenesis of primary hypertension.

Role of Humoral Factors in the Humoral Pathogenesis of Primary Hypertension

Role of Humoral Factors in the Humoral Pathogenesis of Primary Hypertension

Hypertension in Children

The pathogenesis of primary hypertension remains unknown despite extensive investigative contributions. Evidence is mounting that the disease may have its inception in childhood or possibly in infancy. What is needed are long-term longitudinal studies to determine whether the child with primary hypertension eventually becomes the adult hypertensive. A method for the identification of the hypertensive either by specific chemical or physiologic characteristics is very much needed. Nonpharmacologic therapeutic intervention needs careful evaluation, especially in the pediatric patient, to determine whether the disease can be arrested. A thorough study of pediatric patients with primary hypertension should be strongly encouraged. It may be that the solution to the complex puzzle of primary hypertension may have a higher probability of being solved at the inception of the disease in infancy or childhood rather than in the later irreversible stage in adulthood.

Abnormal erythrocyte cation transport in primary hypertension. Clinical and experimental studies.

Several abnormalities concerning sodium (Na+) transport in erythrocytes of essential hypertensive patients have been recently observed. An abnormal extrusion of an erythrocyte Na+ load was described in our laboratory. This defect appeared to be specific for essential hypertension since it was absent in the secondary forms of the disease. The present investigation was performed on 194 Caucasian subjects with essential hypertension or born of hypertensive parents, 86 normotensive controls, and 14 families (78 subjects) studied over two to three generations. The distribution pattern of the erythrocyte defect is compatible with the expression of a single gene transmitted according to an autosomic and dominant mode. To confirm the genetic association between the red blood cell abnormality and primary hypertension, genetically hypertensive rats were investigated in parallel to our clinical studies. A reduction in the net Na+ extrusion from red blood cells was found in two varieties of genetic hypertension (SHR and H-prone-Na+-sensitive Sabra rats). The abnormality could be detected before the development of a significant hypertension. When these various rat sub-strains were acutely or chronically loaded with Na+ (either intraperitoneally or orally), a significant increase in erythrocyte Na+ content was observed only in those substrains having a genetic propensity to develop hypertension. This finding, which appears to be a consequence of the reduction in net Na+ efflux, is of interest for several reasons. It confirms the existence of a close association between a genetic predisposition to develop high blood pressure and cell Na+ retention in the presence of an excess Na+ intake. It draws attention to the possible role of intracellular Na+ in the pathogenesis of primary hypertension. Of more practical importance, the abnormal Na+ handling in erythrocytes may be a genetic marker of primary hypertension.

Raised cerebrospinal fluid norepinephrine in some patients with primary hypertension.

To test whether central neurogenic factors participate in blood pressure elevation in primary hypertension, we studied the concentrations of: norepinephrine, epinephrine and dopamine-beta-hydroxylase (DBH) in cerebrospinal fluid (CSF); and norepinephrine, epinephrine, DBH and plasma renin activity (PRA) in plasma of 22 subjects (seven with primary hypertension, 11 normotensive patients with non-systemic neurological disorders, and four with secondary hypertension). Plasma and CSF norepinephrine (NE) were increased in primary hypertensives compared to normotensives. Cerebrospinal fluid norepinephrine was related to diastolic blood pressure, and systolic blood pressure when normotensive and primary hypertensives were taken together. The CSF norepinephrine of primary hypertensive patients was correlated with natural log PRA. The CSF norepinephrine was correlated inversely with age in primary hypertensive patients but not in the normotensive subjects. The low CSF norepinephrine and epinephrine, despite markedly increased plasma NE and epinephrine, in two patients with pheochromocytoma, indicate a blood-brain barrier for these neurohormones. The observations support the view that the central sympathetic nervous system is involved in the pathogenesis of primary hypertension, particularly in younger patients.