Forms Of Arterial Hypertension Research Articles

ПОЛИМОРФИЗМ ГЕНОВ, УЧАСТВУЮЩИХ В РЕГУЛЯЦИИ ФУНКЦИЙ СОСУДОВ, У ЖЕНЩИН С УГРОЖАЮЩИМИ ПРЕЖДЕВРЕМЕННЫМИ РОДАМИ

Введение. Изучение механизмов возникновения угрозы преждевременных родов имеет большую медицинскую и социальную значимость. В настоящее время в условиях демографического кризиса в России остро встает вопрос о предупреждении невынашивания беременности. Это диктует необходимость проведения дальнейших, в том числе и генетических исследований для наиболее эффективной диагностики и прогноза развития данной патологии. Цель исследования. Изучение особенностей полиморфизма генов системы гемостаза у женщин с физиологическим течением беременности и угрожающими преждевременными родами (ПР) в популяции Ивановской области. Материалы и методы. Обследовано 176 беременных в сроки гестации 22–36 недель в популяции Ивановской области: 73 женщины с физиологически протекавшей беременностью и 103 женщины с угрожающими ПР. Изучали особенности полиморфизмов генов (ADD1 G1378T, AGT T704C, AGT C521T, AGTR1 A1166C, AGTR2 G1675A, CYP11B2-344C/T, GNB3 C825T, NOS3 -786 T/C, NOS3 G894T), участвующих в регуляции функций сосудов. Результаты. Полиморфизмы генов, негативно влияющие на состояние сосудистой стенки, широко распространены у женщин в популяции Ивановской области; ряд полиморфизмов достоверно чаще встречается у пациенток с угрожающими ПР. Вероятно, это может быть причастно к нарушению маточно-плацентарного кровообращения и развитию угрожающих ПР. Заключение. Реализация неблагоприятного генетического фона сопряжена с участием определенных факторов внешней среды, комбинация которых индивидуальна. Introduction. Threatened preterm delivery is a great medical and social problem. At present, prevention of miscarriage is very actual question because of demographic crisis in Russia. So for most effective diagnostics and prognosis of this pathology further genetic investigations are needed. The aim: to study polymorphism of hemostasis-associated genes at women with physiological pregnancy and those with threatened preterm delivery among the population of Ivanovo region. Materials and methods. We examined 176 pregnant women at 22–36 weeks of gestation among population of Ivanovo region: 73 women with physiological pregnancy and 103 women with threatened preterm delivery. We studied the peculiarities of genes polymorphisms (ADD1 G1378T, AGT T704C, AGT C521T, AGTR1 A1166C, AGTR2 G1675A, CYP11B2 -344 C/T, GNB3 C825T, NOS3 -786 T/C, NOS3 G894T) involved in regulation of vascular function. Results. Genes polymorphisms adversely aff ecting the vascular wall are common at women in Ivanovo region; some of polymorphisms signifi cantly are more frequent at women with threatened preterm delivery. Probably this can be responsible for disorders of utero-placental blood fl ow and development of threatened preterm delivery. Conclusion. Realization of adverse genetic background might be caused by unfavorable environmental factors, their combination is individual.

ESSENTIAL SYSTEMIC HYPERTENSION: GENETICS, CLINICS, EXPERIMENT

The lecture is focused on the exploration of genetic and physiological mechanisms of essential systemic hypertension (ESH). A very brief historic review is provided on the first clinical meanings of the ESH. Then some speculation provided, on its etiology, evolutionary-genetic roots regarding the formation of the main BP regulation systems. More detailed, the data is shown on genetic base of hypertensive conditions and ESH. Also, some discussion given on the monogenic forms of arterial hypertension and polygenic fundamentals of ESH, which is the most among hypertension conditions of human. Modern methods considered for genetic origins of ESH evaluation, and a necessity is underlined for the main etiological factors revealing — as of their interrelation for development of rational treatment and prevention methods against ESH.

How can resistant hypertension be identified and prevented?

Resistant hypertension is highly prevalent, and is the form of arterial hypertension that is most difficult to treat. Many patients diagnosed with this disease do not have resistant hypertension, but rather have mismanaged primary hypertension. In many cases blood pressure can be controlled by directly addressing underlying causes such as primary aldosteronism, obstructive sleep apnoea, or excessive neurogenic stimulation. Clinicians should ensure that appropriate blood-pressure measurements are used to diagnose resistant hypertension, explore a variety of drug combinations, and battle clinical inertia. Patients should comply with medication schedules and dietary modifications. Correction of these factors will greatly diminish the prevalence of 'resistant' hypertension and avoid the consequences of a persistently elevated blood pressure in these patients.

Abstract 339: Splice Acceptor Site Mutation in Cullin 3 is Causing Pseudohypoaldosteronism Type II.

A rare Mendelian form of hypertension is Pseudohypoaldosteronism type II (PHAII), also referred to as familial hyperkalemic hypertension (FHHt, OMIM 145260 ). Mutations in WNK1 and WNK4 , and the two recently identified genes KLHL3 and CUL3 have been reported as causes of this monogenic form of arterial hypertension. Mutations in WNK1 and WNK4 result in over-activity of the thiazide-sensitive Na-Cl cotransporter (NCC) in the distal convoluted tubule. In a Turkish family (parents and 5 children) one daughter was suspected of PHAII. This daughter has been diagnosed at age 24 years with severe hypertension (200/130 mm Hg), hyperkalemia (6.5 mmol/l; reference range 3.5-5.1), and normal renal function. Besides a short stature, no other phenotypical abnormalities were identified. The patient’s hypertension and hyperkalemia completely normalized with hydrochlorothiazide, 50 mg daily. All other family members are healthy. Sanger sequencing of WNK1 and WNK4 did not reveal any mutation. A de novo mutation in the daughter is the most likely cause of her disease. Full exome sequencing (Nimblegen SeqCapEZV2, Illumina HiSeq2000) of the seven family members identified 34,733 unique variants in our patient. By comparing the recent mutations reported by Boyden et al, we found an identical de novo mutation in CUL3 , a splice acceptor site mutation in intron 8. RT-PCR analysis of RNA extracted from fresh blood showed two cDNA species in the patient, corresponding to a normal sized CUL3 fragment and an abrogated variant. Sanger sequencing of this shorter form revealed a loss of all nucleotides of exon 9 excluding the first nucleotide and including the first nucleotide of exon 10. This results in an in-frame 57 amino acid deletion abrogating the function of CUL3. After 1 week withdrawal from diuretic medication, we found in the patient’s urinary exosomes, vesicles derived from renal epithelial cells, an increase in the abundance of phosphorylated (P)-NCC (active form) compared to urinary exosomes extracted from urine when using thiazide diuretics. This de novo splice acceptor site mutation found in a second patient with PHAII confirmed CUL3 as a cause of PHAII. This patient also showed up-regulation of P-NCC as reported in WNK1 and WNK4 mutations pointing to the same mechanism of FHHt.

Стан ендотеліальної функції у підлітків із артеріальною гіпертензією

У підлітків із різними формами артеріальної гіпертензії (первинна артеріальна гіпертензія та артеріальна гіпертензія на тлі надмірної маси тіла) вивчено стан ендотеліальної функції. Виявлено, що у підлітків із артеріальною гіпертензією та надмірною масою тіла відбувається формування ендотеліальної дисфункції.

Therapierefraktäre arterielle Hypertonie bei einem jungen Patienten

We report on a 41-year-old patient admitted for refractory arterial hypertension that had developed after a curative chemotherapy regimen due to seminoma stadium IIb four years ago. After exclusion of secondary forms of arterial hypertension (actually unsuccessfully treated with 5 different antihypertensive drugs) we performed a controlled medication intake-trial in our outpatient clinic. 90 minutes after taking the pills the patient complained of dizziness and perspiration while hypotension and bradycardia were measured simultaneously. Due to the difficult psychosocial situation (conflicts with the insurance and in the family, financial problems) and the suspected narcisstic personality disorder the issue of the proven malcompliance was not openly discussed in order to preserve the patient-doctor alliance. The antihypertensive regimen was then reduced to a double regimen. In the second part of the article the most common reasons for refractory arterial hypertension, especially the problem of treatment malcompliance, are summarized.

Characterization of an epitope-tagged guanylyl cyclase-A receptor

Background In some forms of arterial hypertension and as one of the earliest and pathognomonic events in cardiac hypertrophy and insufficiency, the cardiac synthesis and release of ANP and BNP is markedly enhanced, but the GC-A-mediated effects of the NPs are clearly diminished, indicating a receptor or postreceptor defect of GC-A. Thus, from a pathophysiological perspective, identifying the specific mechanisms involved in the downregulation of GC-A activity has important implications. Biochemical studies in transfected GC-A-overexpressing cells showed that phosphorylation of GC-A is essential for its activation process. In turn, inactivation of GC-A probably involves dephosphorylation [1]. NP-dependent activation of GC-A can be reduced not only by chronic exposure to NPs (homologous desensitization) but also by exposure to agents other than NPs (heterologous desensitization). It has been shown in cell culture systems that Angiotensin II and endothelin decrease the responsiveness of GC-A. This is probably mediated by a protein kinase C-induced dephosphorylation of GC-A. However, ultimately the precise posttranslational modifications leading to homologous vs. heterologous GC-A desensitization have not been fully characterized. The present study describes the functional characterization of an epitope-tagged GC-A receptor which might help to enrich the receptor for the characterization of putative posttranslational modifications. Methods, results and conclusion The FLAG (DYKDDDDK) epitope was positioned immediately after the cleavage site of the signal peptide by PCRmediated mutagenesis (pCMV5-FLAG-GC-A) [2]. HEK cells were transfected with cDNAs for GC-A or GC-A tagged with the FLAG epitope.

Arterielle Hypertonie, linksventrikuläre Hypertrophie und ventrikuläre Herzrhythmusstörungen

Patients with hypertensive heart disease have frequently ventricular arrhythmias in the 24-h-holter-EKG. Those patients with severe forms of arterial hypertension have more high grade ventricular tachycardia than those with less severe hypertension. Sudden cardiac death in arterial hypertensive seems to be linked with the prevalence of coronary artery disease, whereas LV hypertrophy is only a co-factor.

Maligne und therapierefraktäre Hypertonie

Early occurences of organ damage, mainly in the cardiovascular system, the central nervous system, of the kidney or the retina, are hallmarks of a malign course in arterial hypertension. Peracute hypertensive emergencies can lead to a rapid deterioration of organ functions, a slower development is observed in patients with therapy-resistant forms of arterial hypertension. In the following article we discuss the historical trends in terminology and epidemiology, clinical symptoms, and possible causes for therapy-resistant hypertension. The latter mainly focuses on possible secondary forms of hypertension and on thoughts on therapy-resistance in primary, idiopathic arterial hypertension, as well as on possible therapeutic approaches.

Vascular and renal function in experimental thyroid disorders

This review focuses on the effects of thyroid hormones in vascular and renal systems. Special emphasis is given to the mechanisms by which thyroid hormones affect the regulation of body fluids, vascular resistance and, ultimately, blood pressure. Vascular function is markedly affected by thyroid hormones that produce changes in vascular reactivity and endothelial function in hyper- and hypothyroidism. The hypothyroid state is accompanied by a marked decrease in sensitivity to vasoconstrictors, especially to sympathetic agonists, alteration that may play a role in the reduced blood pressure of hypothyroid rats, as well as in the preventive effects of hypothyroidism on experimental hypertension. Moreover, in hypothyroid rats, the endothelium-dependent and nitric oxide donors vasodilation is reduced. Conversely, the vessels from hyperthyroid rats showed an increased endothelium-dependent responsiveness that may be secondary to the shear-stress induced by the hyperdynamic circulation, and that may contribute to the reduced vascular resistance characteristic of this disease. Thyroid hormones also have important effects in the kidney, affecting renal growth, renal haemodynamics, and salt and water metabolism. In hyperthyroidism, there is a resetting of the pressure-natriuresis relationship related to hyperactivity of the renin-angiotensin system, which contributes to the arterial hypertension associated with this endocrine disease. Moreover, thyroid hormones affect the development and/or maintenance of various forms of arterial hypertension. This review also describes recent advances in our understanding of thyroid hormone action on nitric oxide and oxidative stress in the regulation of cardiovascular and renal function and in the long-term control of blood pressure.

Hemodynamic and metabolic profile in offspring of malignant hypertensive parents.

Malignant hypertension is a serious form of arterial hypertension in which the physiopathological mechanisms include increased activity of the sympathetic nervous system, renin angiotensin system, and endothelium dysfunction. Family history of hypertension is an important predictive factor for hypertension and is associated with metabolic and hemodynamic abnormalities. Studies of these abnormalities in malignant hypertensive offspring have not yet been published. Therefore, we studied 42 offspring of malignant hypertensive parents (OMH group: age, 22+/-7 years; 23 male subjects; 27 white) and 35 offspring of normotensive parents (ONT group: age, 21+/-4 years; 23 male subjects; 25 white). All subjects had blood pressure <140/90 mm Hg. We evaluated body mass index; office blood pressure; 24-hour ambulatory and continuous beat-to-beat blood pressure monitoring (Finapres); biochemical analysis, including total cholesterol and fractions, triglycerides, glucose, and insulin; and hormonal analysis, including plasma renin activity, aldosterone, and catecholamines. The subjects were also submitted to cold pressure test and handgrip measurements. The body mass index was significantly higher in the OMH group (24+/-5 kg/m(2)) than in the ONT group (22+/-4 kg/m(2)). The OMH group showed significantly higher blood pressure and heart rate in office and Finapres measurements (P<0.05). In 24-hour ambulatory monitoring, the OMH group presented higher 24-hour blood pressure and heart rate, higher blood pressure during the night, and higher heart rate variability during the day compared with those of the ONT group. They also presented lower HDL cholesterol, higher levels of plasma insulin and norepinephrine, and higher insulin-to-glucose ratio (P<0.05) than the ONT group. There were no differences in the other biochemical parameters measured. In conclusion, OMH subjects show early hemodynamic, neurohumoral, and metabolic alterations that are typical of hypertensive metabolic syndrome.

Comparison of urinary excretion of albumin and alpha-1-antitrypsin in patients with arterial hypertension

The aim of the presented pilot study was to compare urinary excretion of two plasma proteins similar in molecular mass and isoelectric point: albumin and alpha-1-antitrypsin (AAT) in patients with different forms of arterial hypertension and in healthy subjects. The 24-h urinary excretion of albumin and AAT were assessed in 52 patients, 29 with essential hypertension and 23 with secondary hypertension, caused by renovascular hypertension, adrenal phaeochromocytoma and obturative sleep apnoea syndrome. The concentrations of albumin and AAT were determined by rocket immunodiffusion. An increase of mean albumin and AAT urinary excretion was demonstrated, as compared to the control group, both in the patients with essential hypertension and with secondary hypertension. In 93.2% of the healthy subjects no AAT presence in urine was detected. No correlation was found between the excretion of albumin and AAT with urine.

Functional reserves of cerebral circulation in patients with arterial hypertension and cerebrovascular insufficiency

765 patients with different forms of arterial hypertension, having cerebrovascular insufficiency, were examined. Correlations of parameters of cerebral and system hemodynamics, microcirculation and functional state of the central nervous system under conditions of controlled physical exercise were studied. The prognostic significance of the early objectivization of initial manifestations of cerebral circulation insufficiency before development of arterial hypertension in preclinical and early clinical stages of brain vascular diseases and the possibil ity of de term in ing functional reserves of cerebral neurodynamics and hemodynamics were shown.

Metabolism of the antihypertensive drug methiapril

Considerable recent attention has been focused on the creation of drugs inhibiting the renin-angiotensin system (RAS) of an organism which are advantageous for treating various forms of arterial hypertension. In screening a broad range of derivatives of piperidinecarboxylic acids, cis-l-(3-acetylthiopropionyl)-6-methylpipecolinic acid was found to be the most efficient inhibitor of the RAS and was named METHIAPRIL (I) [ l ]. In the efficacy and duration of action on various models of arterial hypertension, it is close or superior to the foreign antihypertensive drug CAPTOPRIL (II).

Influence of the renin-angiotensin system stimulation on erythropoietin production in patients with various forms of arterial hypertension.

Recent studies suggest the existence of a relationship between the renin-angiotensin system and erythropoietin (EPO) secretion. It has been studied whether patients with various forms of arterial hypertension (essential, renal, renovascular, in the course of arteritis) differ with respect to EPO secretion and whether EPO serum levels are related to renin response induced by dietary sodium restriction to 10-20 mmol Na/24 h for 3 days and upright body position for 3 h. Patients with different forms of hypertension and normal renal excretory function and healthy subjects did not differ in hematocrit value, markers of iron metabolism, and EPO secretion except for patients with arteritis who had higher ferritin values. In these patients a positive correlation between EPO levels and hematocrit values suggests the existence of an altered regulation of EPO secretion. In essential hypertension a negative correlation found between changes in EPO and PRA levels in response to sodium restriction and upright body position may also reflect an altered regulation of both EPO and renin production.

Cardiovascular function during spinal and epidural anaesthesia: pathogenesis, prophylaxis and therapy of complications

Summary Both spinal and epidural anaesthesia are fraught with a high risk for life-threatening cardiovascular collapse and also fatal cardiac arrests, the incidence of which is higher than with general anaesthesia. These mishaps also endanger young people with sensory block below the T4–T5 range and in spite of appropriate care according to presently accepted standards. With regard to the pathogenesis and also the prophylaxis and therapy of such events, some new information has been considered: 1. Sympathetic neurogenic control of the circulation is impaired, if not completely eliminated, when sensory blockade is above the T6 level (lumbar techniques) or below T6 (segmental thoracic epidural anaesthesia). 2. Major conduction anaesthesia prevents the renin-angiotensin system from acting, so that cardiovascular stability depends entirely on vasopressin. 3. Major conduction anaesthesia primarily reduces central blood volume and thus the heart's filling because of blood pooling in the denervated muscle and skin regions, an effect which is counteracted by vasoconstriction in the remaining innervated body regions and, in the vast majority of people, by constriction of the splanchnic vasculature. 4. Cardiovascular collapse may occur whenever the filling of the heart is further reduced, such as by blood loss, positive airway pressure, or low blood volume states as in certain forms of arterial hypertension or in bed-ridden patients, and also when the vasoconstrictor mechanism of the splanchnic circulation fails in certain individuals with an inherent dysfunction of splanchnic vasomotor control./lt The prophylaxis and therapy of cardiovascular complications during major conduction anaesthesia must primarily be aimed at stabilizing or reestablishing appropriate cardiac filling by an increase in either blood volume or vasomotor tone. There is convincing evidence that the efficacy of vasoconstrictor prophylaxis in preventing cardiovascular complications is by far superior to volume prophylaxis as currently employed. The trouble spot of major conduction blockade resides in the filling of the heart. Vasoconstrictor agents in general and catecholamines of the adrenaline-type in particular mobilize rapidly (within a few minutes at the most) substantial volumes of blood from the peripheral vasculature in favour of the heart. Vasoconstrictors are therefore the first choice for the prophylaxis and therapy of cardiovascular complications during major conduction anaesthesia. It should be remembered that cardiopulmonary resuscitation is ineffective when there is no blood in the heart.

Clinic, diagnosis and treatment of pheochromocytoma in pregnant women

Pheochromocytoma is a catecholamine-producing tumour that arises from the medullary layer of the adrenal gland or extrarenal chromaffin tissue and is not uncommon. An analysis of sectional data published in the world literature in the last two decades shows that pheochromocytoma in 1% of cases; is the cause of hypertension, which in 50-60% of patients runs as a paroxysmal form of arterial hypertension and can progress to a permanent form with or without crises.

Sodium and hypertension. Still a controversy in 1986.

Interpopulation studies support the hypothesis of a causal relationship between sodium consumption and arterial hypertension. However, although this association has been contradicted by intrapopulation studies, the correlation between sodium and hypertension appears to be genetically determined, as there are both sodium-sensitive and sodium-resistant individuals. Sodium is essential for the maintenance of extracellular and plasma volume equilibrium. It is controlled metabolically by the interaction of several biological systems such as the renin-angiotensin-aldosterone system, the sympathetic nervous system and the kallikrein-kinin and prostaglandin systems. Thus, sodium has a definite role in the mechanism involved in the pathophysiology of the predominantly volume-dependent forms of arterial hypertension. Recently, different structural substances with natriuretic effects have been identified. Natriuretic hormone is a non-peptide substance which inhibits the Na,K-ATPase in response to extracellular volume increase. This hormone acts on the renal tubular cells reducing sodium reabsorption, and at an arteriolar level elevating peripheral resistance by increasing smooth muscle tension. Mammalian atria contain various precursors of biologically active peptides, with potent natriuretic and diuretic effects. They are released in response to volume loading and atrial stretch. Although some data suggest an important role for these natriuretic substances in fluid volume and blood pressure control, their place in physiology and in abnormal clinical states should be more definitively clarified in the next few years.

On the structure and forms of arterial hypertension

The problem of the etiological structure of arterial hypertension continues to attract the attention of researchers.

Evidence of altered structure of the erythrocyte membrane in spontaneously hypertensive rats.

1. The membrane structure of erythrocytes of rats with different forms of arterial hypertension was studied by means of two hydrophobic fluorescent probes (diphenylhexatriene and pyrene). 2. Microviscosity of hydrophobic areas of erythrocyte membrane of spontaneously hypertensive rats was found to be increased compared with that of membranes from normotensive control rats. 3. No alterations of membrane structure of erythrocytes of deoxycorticosterone-treated rats and renal hypertensive rats were found.