Genesis Of Essential Hypertension Research Articles

Çocukluk çağı primer hipertansiyonuna etki eden faktörlerin araştırılması

Aim: Primary hypertension is the most important risk factor for chronic kidney disease in adulthood. The genesis of essential hypertension is likely to be multifactorial. The aim of this study is to investigate the causing factors of primary hypertension detected by ambulatory blood pressure monitoring in children.Materials and Methods: Fifty-six patients who had blood pressure higher than 90 percentile during the healthy children follow-up and 27 healthy children with the normal blood pressure were included in the study. Twenty-four hour blood pressure measurements with the blood pressure monitor were recorded as the day-night mean blood pressure, the blood pressure loads and the dipper-non-dipper characteristics. Plasma renin levels, serum aldosterone, nitric oxide and endothelin levels and amounts of sodium and potassium excretion in the 24 hour urine and were investigated in all patients and the control group.Results: Laboratory evaluations of the patients showed that the patient group has higher mean levels of plasma renin, lower mean levels of blood endothelin and mean levels of urinary sodium excretion than the control group.Conclusion: In the pathogenesis of childhood primary hypertension and white coat hypertension, which were seen in the half of the children diagnosed as primary hypertension, plasma renin and urinary sodium excretion had important roles.

HYPERTENSION CAUSED WITH URIC ACID – THERAPEUTICAL MODALITIES

The paper presents a patient who was first diagnosed with hypertension just a few days before developing gout. Hypertension occurred along with the hyperuricemia last year after curing the patient of gout. Hyperuricemia was initially symptomatic and manifested as gout; later it was without its specific symptoms but was always associated with hypertension. Just a month after correction of the patient’s previous diet, the levels of uric acid and blood pressure were normal or at pre-hypertensive values. Our case supports the concept of the predictive role of uric acid in the genesis of essential hypertension and emphasizes the application of an adequate diet in the therapy of some forms of hypertension. Acta Medica Medianae 2011;50(3):49-53.

Essential hypertension in adolescents and children: Recent advances in causative mechanisms

Essential hypertension is the most common form of hypertension in adults, and it is recognized more often in adolescents than in younger children. It is well known that the probability of a diagnosis of essential hypertension increases with age from birth onward. The initiation of high blood pressure burden starts in childhood and continues through adolescence to persist in the remaining phases of life. The genesis of essential hypertension is likely to be multifactorial. Obesity, insulin resistance, activation of sympathetic nervous system, sodium homeostasis, renin-angiotensin system, vascular smooth muscle structure and reactivity, serum uric acid levels, genetic factors and fetal programming have been implicated in this disorder. In addition, erythrocyte sodium transport, the free calcium concentration in platelets and leukocytes, urine kallikrein excretion, and sympathetic nervous system receptors have also been investigated as other possible mechanisms. Obesity in children appears to be the lead contributor of essential hypertension prevalence in children and adolescents. Suggested mechanisms of obesity-related hypertension include insulin resistance, sodium retention, increased sympathetic nervous system activity, activation of renin-angiotensin-aldosterone, and altered vascular function. The etiopathogenesis of essential hypertension in children and adolescents appears to closely resemble that of adults. The minor variations seen could probably be due to the evolving nature of this condition. Many of the established mechanisms that are confirmed in adult population need to be replicated in the pediatric age group by means of definitive research for a better understanding of this condition in future.

Marinobufagenin may mediate the adverse impact of salty diets on renal calcium retention by impairing the efficiency of renal tubular sodium–calcium exchange

For reasons yet to be clarified, salt loading and plasma volume expansion decrease renal calcium retention; consequently, high-salt diets are thought to increase risk for osteoporosis and renal stones. These measures also can evoke increased adrenal production of the natriuretic factor marinobufagenin (MBG), recently implicated in the genesis of essential hypertension. MBG achieves natriuresis via potent selective inhibition of the alpha-1-type sodium pump, expressed throughout the nephron. In as much as renal calcium retention is largely dependent on efficient activity of calcium-sodium exchangers situated in the basolateral membranes of tubular epithelium, it is evident that an increased intracellular sodium concentration consequent to sodium pump inhibition could blunt the activity of these exchangers. Thus, it is postulated that MBG mediates the impact of salt loading on renal calcium retention.

Lipoprotein lipase gene is in linkage with blood pressure phenotypes in Chinese pedigrees.

To elucidate the mechanism of lipid metabolism in the genesis of essential hypertension (EH), we linked blood pressure (BP) phenotypes with the lipoprotein lipase (LPL) gene. Variance component and sib-pair linkage models were used to test the relationship of the polymorphisms in the LPL gene region and EH in 148 Chinese hypertensive families. Linkage evidence with systolic BP (SBP) and diastolic BP (DBP) was observed in a total population of 148 pedigrees with seven flanking microsatellite markers of the LPL gene, with a maximum two-point LOD score of 2.68 and a maximum multipoint LOD score (MLS) of 2.37 for SBP and a maximum MLS of 1.54 for DBP. Suggestive linkage results around this region were also obtained in northern and southern subsets by geographic distribution. In addition, quantitative-transmission/disequilibrium-test analyses showed that there was linkage between DBP and two single nucleotide polymorphisms in the LPL gene. This is the first report of linkage between LPL gene and DBP in the Chinese population. The LPL gene itself might explain our results or the LPL gene region might harbor some genes to explain the observed results to some degree and might contribute to the variation of BP in the Chinese population.

Relationship between lipoprotein(a) levels, oxidative stress, and blood pressure levels in patients with essential hypertension.

High plasma levels of lipoprotein(a) [Lp(a)] are considered a risk factor for the development of coronary artery disease. In vitro experiments have shown that oxidized Lp(a) is able to impair the arterial endothelium-dependent dilation, thus suggesting a possible role of Lp(a) in the genesis of essential hypertension. The aim of our work was to investigate the correlation of blood pressure levels with plasma Lp(a) concentration, apo(a) isoform size, and peroxidative stress in patients with essential hypertension. The study was performed in 54 untreated hypertensive patients whose blood pressure was monitored for 24 h by ambulatory blood pressure monitoring. Lp(a) concentration was measured by a double monoclonal antibody-based enzyme immunoassay demonstrated to be insensitive to apo(a) size heterogeneity. Apo(a) isoforms were determined by a high-resolution SDS-agarose gel electrophoresis followed by immunoblotting. A significant correlation was found between Lp(a) levels and the night-time systolic and diastolic pressures (r=0.32, P<0.05 and r=0.30, P<0.05, respectively), as well as with the mean night-time fall in systolic and diastolic blood pressures (r=-0.28, P<0.05 and r=-0.29, P<0.05, respectively). These relationships were further potentiated when peroxidative stress data were taken into consideration (r=0.37 and r=0.40, P<0.01 for the night-time systolic and diastolic pressures, respectively and r=-0.34 and r=-0.38, P<0.01 for the night-time fall in systolic and diastolic blood pressures, respectively). Apo(a) isoform size did not affect these relationships. Our data suggest that Lp(a) and peroxidative stress may be involved as cofactors in essential hypertension, with a mechanism that remains to be elucidated.

Lower body nerve stretch: A role in essential hypertension or pre-eclampsia?

Despite the relatively high incidence of essential hypertension and pregnancy-induced hypertension, the etiologies of these disorders remain enigmatic. A link between stretching of neural structures in the lower body and the induction of hypertension in these disorders in hypothesized. Hypertension has been documented in patients undergoing femoral and tibial lengthening procedures; in experimental models the stretching of lower extermity nerves appeard to be responsible for the increase in blood pressure with bone lengthening. The upright posture of humans puts an added strain on nerves and an increased pressure on lumbar disks may put increasingly tension on the nerve roots. The resultant nerve stretch in pregnant women may be exacerbated by the hormone relaxin. A possible link between the stretching of neural structures and the genesis of essential hypertension or pre-eclampsia.eclampsia is hypothesized.

Assessment of autonomic nervous function in human hypertension.

In spite of the popular belief that "nervous tension," "stress," and hypertension are causally related, it has been difficult to prove a role of autonomic dysfunction in the genesis of essential hypertension. There are three major reasons for this: 1) autonomic function cannot be assessed with one simple test, 2) the short-term "phasic" and long-term "tonic" autonomic control of blood pressure are not necessarily interrelated, and 3) hypertension is a dynamic process in the course of which there are changes in autonomic control. Some of the controversies in the field stem from the lack of appreciation of these limitations.

Renal consequences of arterial hypertension

To seek ways of improving the prognosis for renal function in the presence of arterial hypertension. Nephrosclerosis is a term used to define the renal damage induced by arterial hypertension. The renal vasculature can participate in the genesis of essential hypertension and can suffer the consequences of elevated blood pressure. There is no doubt that antihypertensive therapy has dramatically improved the prognosis for renal function in the presence of arterial hypertension. There appears to be a need for a further improvement in the prognosis for renal hypertension. At present, the prevalence of nephrosclerosis as a cause of terminal renal failure may be increasing and a progressive fall in renal function in treated hypertensive patients compared to normotensives has been described. It is not yet clear whether improvements in renal hypertension depend merely on the effectiveness of antihypertensive therapy in reducing arterial blood pressure or whether it will be necessary to improve the metabolic disturbances that accompany hypertension or the renal hemodynamic effects of different drugs before the prognosis for nephrosclerosis can be improved.

Roles of sodium, potassium, calcium, and natriuretic factors in hypertension.

This review first summarizes evidence from animals and humans for and against a role for dietary sodium in the genesis and treatment of hypertension. The evidence for its role is strongest in those subjects with impaired ability to excrete sodium because of organic renal disease or mineralocorticoid excess. Here, restriction of dietary sodium promptly lowers pressure. Its role in the genesis of essential hypertension is more controversial. Nevertheless, it appears that some patients with mild to moderate essential hypertension respond to moderate sodium restriction with a modest fall in pressure. This restriction also seems to reduce the amount of antihypertensive medication needed to keep pressure under control. Next, the mechanism of the pressure response to dietary sodium chloride is considered, with emphasis on potassium depletion and increased plasma levels of prohypertensive sodium pump inhibitor and antihypertensive atrial natriuretic peptide. The evidence for a primary role for dietary potassium in the genesis of hypertension then is summarized; certain subsets of subjects with a high incidence of hypertension also have a lower potassium intake. Some investigators have found that dietary potassium supplementation lowers pressure in established hypertension. This may result from natriuresis and from vasodilation subsequent to stimulation of Na+,K(+)-ATPase in vascular smooth muscle and adrenergic nerve terminals. After the role of dietary calcium is discussed, practical aspects of dietary sodium restriction and dietary potassium supplementation in the therapy for established hypertension are considered. The review concludes with comments on their possible roles in the prevention of hypertension.

Dietary sodium and potassium in the genesis, therapy, and prevention of hypertension.

In this review, we first summarized the evidence from animals and man for and against a role for dietary sodium in the genesis and treatment of hypertension. The evidence for a role for dietary sodium in the genesis of hypertension is strongest in those subjects with impaired ability to excrete sodium due to organic renal disease or mineralocorticoid excess. Here restriction of dietary sodium promptly lowers arterial pressure. Its role in the genesis of essential hypertension is still controversial. Nevertheless, it appears that some patients with mild to moderate essential hypertension respond to moderate sodium restriction with a modest fall in blood pressure. This restriction also seems to reduce the amount of antihypertensive medication needed to keep blood pressure under control. We next considered the mechanism of the pressure response to dietary sodium chloride, concentrating upon the increase in extracellular fluid volume, potassium depletion, and increased plasma levels of prohypertensive sodium pump inhibitor and antihypertensive atrial natriuretic factor. We next summarized the evidence for a primary role for dietary potassium in the genesis of hypertension and pointed out that certain subsets of subjects with a high incidence of hypertension also have a lower dietary potassium intake. Some investigators find that dietary potassium supplementation lowers blood pressure in established hypertension. This may result from natriuresis and from vasodilation subsequent to stimulation of Na+, K+-ATPase in vascular smooth muscle and adrenergic nerve terminals. We then considered practical aspects of dietary sodium restriction and dietary potassium supplementation in the therapy for established hypertension. The review concludes with comments on their possible roles in the prevention of hypertension.

Systemic compliance: does it play a role in the genesis of essential hypertension?

Arterial compliance is part of the load faced by the heart. Decreased compliance increases this load. We have studied the cardiovascular consequences of decreased systemic compliance in six closed chest anaesthetised dogs where ascending aortic flow transducers and left ventricular crystals had previously been implanted. A stiff tube was put into the abdominal aorta from the left flank and moved to the ascending aorta. Inflation of a cuff on the proximal end of the tube forced the heart to eject into a non-compliant outflow conduit. The distal end of the tube was connected to the distal aorta and, via a pump, to a carotid artery where mean pressure was kept above 80 mmHg. We measured systemic pressures (catheter-tip manometer), cardiac output (electromagnetic flowmeter) and either left ventricular end-diastolic pressure (fluid filled catheter, Statham P23Db) or left ventricular diameter (ultrasound transit time method). From these variables we calculated systemic compliance and input impedance. A 35% decrease in compliance caused a 12% increase in systolic, and a 12% decrease in diastolic pressure while mean pressure and cardiac output did not change significantly. With a decrease in compliance of 63% systolic pressure increased by 18%, while diastolic pressure decreased by 24%. Mean pressure did not change significantly but cardiac output fell by 21%. In both groups of altered compliance peripheral resistance rose slightly but this was not significant. Decreased compliance mainly caused changes in the low frequency range of the input impedance: moduli increased and phase angles became more negative.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of digoxin on responsiveness to the pressor actions of angiotensin and norepinephrine in man.

Abnormalities in sodium metabolism, including the presence of endogenous circulating digitalis-like sodium transport inhibitors, have been implicated in the genesis of essential hypertension. Digitalis has also been reported to affect adrenal steroid output in vitro. We studied the effects of 4 days of treatment with the digitalis glycoside digoxin upon blood pressure, the renin-aldosterone axis, and pressor and steroidogenic responses to graded norepinephrine, angiotensin, and ACTH infusions in six normal men after pretreatment with dexamethasone. Digoxin produced no significant changes in blood pressure, urinary electrolyte or aldosterone excretions, PRA or aldosterone concentrations, or the incremental responses of aldosterone or cortisol to angiotensin or ACTH. However, digoxin significantly augmented pressor responsiveness to both norepinephrine and angiotensin without significantly affecting the steady state baroreceptor-heart rate reflex. These findings support the hypothesis that digitalis-like factors may have important effects upon arterial blood pressure control in man.

Endocrine Pharmacology of SHR (Report 5) : Retardation in the development of spontaneous hypertension by gonadectomy before or after adrenal enucleation

Spontaneously hypertensive male rats (SHR) of Kyoto-Wistar (KW) strain were divided into 3 groups : castration (cast) performed at 4 weeks old (W) and adrenal enucleation (enucl) at 10 W as group 1, cast at 4 W and enucl at 22 W as group 2, and enucl at 10 W and cast at 22 W as group 3. Systolic blood pressure (BP) was measured by an indirect tail cuff method. Group 1:4 W cast rats showed a significantly lower BP as compared with intact SHR up to 22 W ; 10 W enucl rats showed a significantly higher BP over intact SHR up to 22 W ; and cast plus enucl rats showed a significantly higher BP over cast only-rats, but they showed a significantly lower BP compared to enucl only-rats. Group 2 : Rats bearing cast at 4 W and enucl at 22 W manifested progressively significantly BP, and values reached a level comparable to that of cast plus enucl rats as shown in group 1. The BP of these two groups were significantly below those of intact SHR until 35 W. Group 3 : Rats that received enucl at 10 W showed significant elevation in BP over the intact SHR up to 22 W ; but BP did not rise following cast at 22 W, and the BP was significantly below that of enucl only-rats. These values reached a level comparable to that of intact SHR. These results suggest that 1) enucl in the presence or absence of gonad increases significantly BP in both SHR and KW, 2) gonadectomy decreases significantly BP in enucl SHR and retards significantly BP in intact SHR ; however, 3) gonadectomy did not alter the BP in KW rats. It is concluded that gonad or gonadal hormones play an important role in the genesis of essential hypertension.

A circulating inhibitor of (Na+ + K+)ATPase associated with essential hypertension.

The aetiology of essential hypertension, a disease prevalent in cultured societies, is unknown. However, much evidence suggests that abnormal sodium metabolism has a critical role—this has led to the hypothesis that an increase in the circulating concentration of an inhibitor of (Na+ + K+) ATPase is responsible for the increased peripheral vascular resistance in essential hypertension1. Evidence for relatively high levels of a Na+ pump inhibitor in essential hypertension has come from bioassay and cytochemical assays of plasma and urine from normotensive and hypertensive individuals2,3. There is also evidence for increased plasma levels of a Na+ pump inhibitor in some animal models (for example, renal and deoxycorticosterone acetate (DOCA) models) of hypertension4. Nevertheless, direct biochemical determination of (Na+ + K+) ATPase inhibition by this substance has not yet been reported. We demonstrate here, with a kinetic (Na+ + K+) ATPase assay, a highly significant correlation between levels of a plasma inhibitor of (Na+ + K+)ATPase activity and mean arterial blood pressure (MAP) in normotensive and hypertensive individuals. These data provide evidence for the involvement of a circulating Na+ pump inhibitor in the genesis of essential hypertension. Moreover, our assay methods may be useful for the isolation and characterization of this inhibitor.

A primary role for vasopressin in the genesis of essential hypertension.

Alterations in the renin-angiotensin system are caused by changes in the vascular perfusing pressures in the renal outer cortex. The renal peripheral resistance to the perfusing pressures in the renal outer cortex is to some extent controlled by the plasma sodium load, sympathetic, and vasoconstrictor stimuli. Logically, therefore, the renin-angiotensin system can be excluded from any primary involvement in the genesis of essential hypertension. Because high plasma renin hypertension inevitably progresses to organic vascular involvement, it is clear that angiotensin-ii plays an important vasoconstrictor role at some later stage. Experiments, involving Goldblatt techniques, which alter the renal perfusion pressure and hence activate the renin-angiotensin system, skip over a preliminary period during which, under natural conditions, unknown factors are slowly inducing an increase in the total peripheral resistance. It is argued that the dominant natural factor during this preliminary period is an excess general vasotonic influence exerted by vasopressin.It is argued that essential hypertension develops in those individuals who, for some reason, over a long period of time intermittently release excessive amounts of vasopressin and who also possess a particularly hyper-reactive renal-adrenal feed-back system. Built into this system is the capability of activating a catecholamine overdrive postulated by several authors as an important, though secondary factor, in the development of essential hypertension.

The role of vascular capacitance in the genesis of essential hypertension.

1. Analysis of relationships between blood volume, vascular capacitance, cardiopulmonary and peripheral blood volumes, labelled albumin disappearance rate, plasma renin activity, blood pressure and age was performed in essential hypertensive males. 2. The results indicate that capacitance bed constriction probably occurs with age in essential hypertension leading to an increase in the product blood volume xvascular capacitance tone even in the presence of low blood volume. 3. A metabolic defect in the venous vascular bed along with an abnormality of regulation of renal sodium excretion is postulated.

Excretion of 3H-norepinephrine in the urine of hypertensives

The role of catecholamine-sympathetic nervous system on the genesis of essential hypertension has long been investigated, but unsettled. Ikoma reported an increase of norepinephrine excretion in the urine of patients with essential hypertention without renal insufficiency, whereas Euler demonstrated elevated levels of urinary excretion of norepinephrine in only 16.4 per cent of 500 hypertensive patients. There were also no significant differences in urinary excretion of the metabolites of catecholamines between normal controls and hypertensive patients. On the other hand, the fact that most antihypertensive agents currently used are involved in some way with catecholamine metabolism, suggests an intimate relationship between hypertension and sympathetic nervous system. Gitlow was the first who investigated the catecholamine metabolism of the essential hypertension with use of dl-beta-H3-norepinephrine. It was assumed that the accelerated turnover of norepinephrine may be present in the essential hypertensive patients. However, De'Quattro could not confirm the accelerated turnover in the hypertensive patients. This discrepancy may be the reflection of the absence of a uniform sympathetic nervous response in the different varieties of hypertension. There are posturated two stages of essential hypertension, i.e., labile and fixed. A heightened sympathetic and circulatory activity may be more characteristic in the early labile than in the fixed phase of essential hypertension. The purpose of this study was to compare the rate of norepinephrine turnover in labile hypertension and fixed hypertension and to study on the effect of fusaric acid, a potent inhibitor of dopamine beta hydroxylase, on the catecholamine turnover in the hypertensive patients.

Isolation of a polar aldosterone-like substance from the urine and adrenal incubates of patients with arterial hypertension.

A CONJECTURED role of disordered sodium-retaining function of the adrenal cortex in the genesis of essential hypertension has been largely founded on indirect evidence1,2, including the rationale of low-sodium intake3,4 and of naturetic agents5,6 in therapy; and on direct steroid measurements7,8. These latter have shown hyper-excretion of the mineralocorticoid, aldosterone (11β,21-dihydroxy-20-oxo-pregn-4-ene-18-al), arid its major metabolite, tetrahydroaldosterone (3α, 11β,21-trihydroxy-20-oxo-5β-pregnane-18-al), in uncomplicated as well as complicated forms of this disease. These observations have favoured the hypothesis that essential hypertension may represent, in effect, a special form of hyperadrenocorticism. Correlation of normal aldosterone regulation with the renin-angiotensin mechanism in the kidney9,10 has further focused attention on possible regulatory abnormalities of aldosterone in the pathogenesis of arterial hypertension.

Evaluation of l-hydrazinophthalazine (apresoline) in treatment of hypertensive disease.

DEMONSTRATION of a humorally mediated pressor mechanism of centralnervous origin1prompted the suggestion that this system might sometimes participate in the genesis of essential hypertension. Since the pressor effect was suppressed by apresoline (1-hydrazinophthalazine, Ciba), it was considered possible that patients in whom the mechanism was operative would respond favorably and relatively specifically to treatment with this drug. It was recognized that the drug has properties which might tend to decrease arterial pressure by other means than inhibition of cerebral pressor activity. With these considerations in mind, a survey was initiated of the therapeutic effects of apresoline when administered as the sole antipressor agent to patients suffering from a wide spectrum of hypertensive disease. METHOD OF STUDY Ninety-seven patients were treated with apresoline for at least 3 months and usually for 12 months or more. Of these, 58 were hospitalized for close observation and at least preliminary treatment; as