[Aldosterone as an endogenous cardiovascular toxin and the options for its therapeutic management]. / Aldosteron jako endogenní kardiovaskulární toxin a moznosti jeho terapeutického ovlivnení.

In physiological, as well as pathological situations, aldosterone significantly influences volume, pressure and electrolyte balance. Primary hyperaldosteronism is caused by autonomous over-production, most frequently due to adrenal adenoma. Patients with primary hyperaldosteronism (Conn's syndrome) have more pronounced left ventricular hypertrophy and higher frequency of cardiovascular events than patients with essential hypertension (EH) with comparable blood pressure values. Consequently, there is an increased interest in the role ofaldosterone tissue function in cardiovascular disease. The aim of the present paper is to emphasise the pleiotropic actions of aldosterone on cardiovascular system and the options for their therapeutic management. Apart from the effects of circulating aldosterone on BP and its renal actions on water and electrolyte excretion, extra-renal effects are also been explored; paracrine affects through tissue mineralocorticoid receptors (MR) may impact on endothelial dysfunction, vascular elasticity, inflammatory changes in the myocardium, vessels and kidneys. Initial oxidative stress due to increased aldosterone concentrations may initiate subclinical endothelial changes and subsequent myocardial fibrosis. The effects on all three layers of vascular wall, together with increased blood coagulation and vascular thrombogenicity increases likelihood of microthrombosis and tissue microinfarctions. Slight increase in aldosterone concentrations in cardiac tissue adversely affects myofibrils as well as coronary artery function. Similar to peripheral vessels, it increases collagen content and changes vascular rigidity and the velocity of pulse wave and facilitates development of perivascular fibrosis. Higher salt intake may potentiate these pathophysiological effects of aldosterone, while higher intake of potassium may restrict them. Aldosterone vasculopathy together with perivascular fibrosis occurring at aldosterone concentrations seen with heart failure contributes to manifestation of heart failure. Consequently, aldosterone may rightly be called "cardiovascular toxin". The adverse effects of aldosterone in patients on long-term ACEI therapy are further facilitated by the aldosterone's ability to evade inhibitory effects of ACEI and parallel activation of renin-angiotensin system. To manage these situations, receptors of mineralcorticoids or direct renin inhibitor aliskiren are used. The positive effect of MR blockade is based on an increased release of nitric oxide (NO) with further improvement in endothelial functions. Detailed review of pleotropic effects of aldosterone helps to clarify a number of pathophysiological situations in essential hypertension, supports the view ofaldosterone as a potential cardiovascular toxin and indicates the use of mineralocorticoid receptor blockers in resistant hypertension and patients with cardiovascular or renal organ damage.

Association of the -344T/C aldosterone synthase gene variant with essential hypertension.

The aldosterone synthase gene (CYP11B2) is an important candidate gene region in essential hypertension. We therefore studied the association of -344T/C polymorphism of the CYP11B2 gene with the presence and severity of hypertension in a case-control study. We studied 369 individuals, of whom 213 were hypertensive patients (139 controlled hypertensive, 74 resistant hypertensive) and 156 were healthy normotensive subjects. The -344T/C polymorphism of the CYP11B2 gene was determined using polymerase chain reaction - restriction fragment length polymorphism analysis. The distribution of genotypes in normotensive controls and hypertensive subjects were: TT 25.6 vs. 31.9 %, TC 51.9 vs. 57.3 % and CC 22.4 vs. 10.8 %. The -344T/C variant was associated with hypertension. Subjects carrying the -344T allele had a greater risk of hypertension compared to those having C allele (chi(2)=5.89, p<0.05). The frequency of CC genotype was significantly lower in hypertensive patients than in normotensive controls (chi(2)=9.44, p<0.01). A stepwise logistic regression analysis confirmed these findings. We did not find an association of -344T/C variant with the resistance of hypertensive patients to combination therapy, but we observed an association of -344T/C polymorphism of aldosterone synthase gene with increased risk of hypertension. These results support a potential role of -344T/C CYP11B2 gene polymorphism in genetic predisposition to develop hypertension.

[Reducing food salt content--a neglected approach to hypertension prevention and treatment in the population]. / Snízení obsahu soli v potrave--opomíjený postup v prevenci a lécbe hypertenze v populaci.

Long-term dietary salt supply, disproportional to the high metabolic requirements, plays an important role in pathogenesis of arterial hypertension. BP, its rise with age and hypertension prevalence in the population are directly proportional to sodium supply. Consistent effect of salt supply on the BP values is documented from observational as well as randomised controlled studies. It is, therefore, possible to assume that decrease in salt intake in the population could positively affect population BP mean, age-related increase in BP as well as a range of cardiovascular complications of hypertension and could thus contribute to improving the course and prognosis of this "non-infectious epidemy", the incidence of which exceeds 30% in the adult population and increases continually with age. Based on a review of published population-based observations and clinical studies, the paper summarizes briefly the opinions on the impact of the sodium chloride dietary intake modifications on BP, outcomes of these modifications within various historical, ethnic, experimental and clinical contexts, impact on BP morbidity and mortality, population-based importance of the current high salt supply decrease on these indicators and possible utilization in the primary prevention of hypertension.

Genetics of Cd36 and the clustering of multiple cardiovascular risk factors in spontaneous hypertension.

Disorders of carbohydrate and lipid metabolism have been reported to cluster in patients with essential hypertension and in spontaneously hypertensive rats (SHRs). A deletion in the Cd36 gene on chromosome 4 has recently been implicated in defective carbohydrate and lipid metabolism in isolated adipocytes from SHRs. However, the role of Cd36 and chromosome 4 in the control of blood pressure and systemic cardiovascular risk factors in SHRs is unknown. In the SHR. BN-Il6/Npy congenic strain, we have found that transfer of a segment of chromosome 4 (including Cd36) from the Brown Norway (BN) rat onto the SHR background induces reductions in blood pressure and ameliorates dietary-induced glucose intolerance, hyperinsulinemia, and hypertriglyceridemia. These results demonstrate that a single chromosome region can influence a broad spectrum of cardiovascular risk factors involved in the hypertension metabolic syndrome. However, analysis of Cd36 genotypes in the SHR and stroke-prone SHR strains indicates that the deletion variant of Cd36 was not critical to the initial selection for hypertension in the SHR model. Thus, the ability of chromosome 4 to influence multiple cardiovascular risk factors, including hypertension, may depend on linkage of Cd36 to other genes trapped within the differential segment of the SHR. BN-Il6/Npy strain.

[Does the rennin inhibitor aliskiren offer promising novel opportunities in the treatment of cardiovascular diseases?]. / Predstavuje inhibitor reninu aliskiren nové výhledové moznosti v lécbe kardiovaskulárních onemocnení!

The renin-angiotensin-aldosterone system (RAAS) plays an important part in the pathogenesis of arterial hypertension and the complications it causes in organs (the heart, the circulatory system, the brain, the kidneys), heart failure and kidney diseases. Materials that block the most upstream point of the RAAS cascade (ACE inhibitors - ACEI, AT1,-receptor (AT1R) blockers, aldosterone receptor blockers) have greatly expanded our options in the treatment and primary and secondary prevention of cardiovascular and renal diseases. ACEI and AT1R blockers interrupt the normal feedback provided by the release of renin into the circulatory system from the kidneys. After they are applied the reactive increase in active circulating renin leads to increased creation of angiotensin I and angiotensin II and the subsequent return of aldosterone secretions to pre-treatment values ("escape" phenomenon). The possible negative effect of these intermediary products of an incomplete blockade of RAAS on organ complications lead to an effort to develop a material that could block the renin-angiotensin cascade at its first stage--i.e. a renin blocker. The first efforts with renin antibodies or peptide analogues of renin prosegments failed to satisify the basic requirements for long-term medication--effectiveness when used orally. In recent years the first non-peptidic, oral renin ihibitor providing sustained effects has been developed, aliskiren fumarate. Aliskiren reduces BP depending on the dose (50-300 mg/day) in monotherapy or in combination with hydrochlorothiazide. Aliskiren lowers plasma renin activity (PRA) and neutralises the activation of the RAAS triggered by hydrochlorothiazide. Ambulatory BP monitoring has shown that taking the medicine once a day has a 24-hour effect and its continued residence in the kidneys suggests renoprotective effects. The compound is in the third stage of clinical tests as a monotherapy or in combination for the treatment of hypertension. It has also been shown to have an influence on the regression of cardiac hypertrophy (Aliskiren in Left-Ventricular Hypertrophy trial - ALLAY), the treatment of heart failure (Aliskiren Observation of Heart Failure Treatment trial - ALOFT) and diabetic (Aliskiren in the Evaluation of Proteinuria in Diabetes trial - AVOID). In April 206, the FDA permitted the use of aliskiren in the USA for the treatment of high BP and it is currently undergoing testing in Europe. The renin inhibitor has minimal undesirable side effects, like AT1-receptor blockers. The slightly lower effectiveness ofaliskiren than AT1-receptor blockers in reducing BP is caused by the fact that it does not block bradykinins. It is recommended as a monotherapy for clinical use or in combination with other antihypertensive medicines for conditions with high levels of PRA including its rise after diuretics, ACEI and AT1-receptor blockers. Aliskiren could therefore be used primarily with young patients, Caucasians, persons with ACEI intolerance, and also in diseases where angiotensin II is involved in the pathogenesis and the secondary prevention of cardiovascular disease. It is also safe for persons with concurrent renal problems, because it is mainly removed by the liver without great interference with other materials. Like ACEI, the renin inhibitor has a vasodilatory effect which could potentially improve the elasticity of arteries. The medicine has the same limitations and contraindications as ACEI and AT1R blockers, such as pregnancy and bilateral renal artery stenosis. A definitive assessment of the benefit of this new class of medicines and its broad application in the treatment of cardiovascular and other diseases will require demonstration of its long-term effect on morbidity and mortality, as well as comparison with other RAAS blockers in long clinical studies, which represent research programmes lasting another 7 to 8 years.

[Nitric oxide synthase, typical flavohemoproteins and their complicated enzymology]. / Syntázy oxidu dusnatého, typické hemoflavoproteiny a jejich komplikovaná enzymologie.

Nitric oxide is a diatomic gaseous molecule with unpaired electron in the molecule. Physical properties such as solubility, diffusibility and half-life decide the chemical reactivity of nitric oxide. Nitric oxide is the unstable free radical in vessels, immune system and central nervous system. The reactivity of nitric oxide under physiological and pathological conditions depends upon its concentration and site of production. Nitric oxide is thought to play a role in many pathological situations: septic shock, cardiovascular diseases, arthritis, diabetes, multiple sclerosis, asthma, and hypertension. Nitric oxide synthase is a self-sufficient flavohemoprotein capable of producing nitric oxide from L-arginine by two successive monooxygenation steps. Although the N-terminal heme domain functionally resembles cytochromes P450, no structural similarities exist between cytochrome P450 and nitric oxide synthases heme domains. The C-terminal domain of nitric oxide synthases containing flavin adenine dinucleotide and flavin mononucleotide as cofactors exhibits a high degree of sequence similarity with NADPH-cytocrome P450 reductase. The reductase domains serve as an intermediary for the transfer of electrons from NADPH for the catalytic reaction. The connecting domain between the oxygenase and the reductase domains of nitric oxide synthase isoforms binds calmodulin in the presence of calcium. The binding of calmodulin to all nitric oxide synthase isoforms is obligatory for the production of nitric oxide. At the same time, the presence of one or more phosphorylation sites in nitric oxide synthase puts them among the kinase-mediated signaling pathways. This also means that nitric oxide synthases are regulated indirectly by the events that regulate kinases. This field of research of nitric oxide synthase regulation has become one of the most actively pursued and much has been learned from basic biochemical mechanisms to physiological processes and to medical applications, but many more questions still remain to be answered.

[Recommendations for the treatment of tobacco dependence]. / Doporucení pro lécbu závislosti na tabáku.

This first Czech version of guidelines formulated by the working group of mentioned medical associations is based on current literature and international guidelines. They are aimed mainly on clinical medicine and on incorporation of this treatment into the health care system according to WHO recommendations. They should serve to the treatment of tobacco dependence at any level: during any contact with the smoking patient (short intervention), in specialised centres or for the health care providers or health system itself.

Blood pressure, endothelial function and circulating endothelin concentrations in liver transplant recipients.

OBJECTIVES: To study candidates for liver transplant before and 6 weeks after transplant, and to elucidate the role of endothelial dysfunction and plasma endothelin concentrations in the development of hypertension. DESIGN PROSPECTIVE: follow-up study. SETTING: Institutional, outpatient. PATIENTS: and controls Fifteen patients (11 men, four women, mean age 46.7+/-13.2 years) with end-stage liver disease (ESLD) and healthy volunteers of comparable age and sex. METHODS: We performed office blood pressure readings and 24 h ambulatory blood pressure monitoring (ABPM), measurements of endothelial-dependent vasodilatation using high-resolution ultrasound in the brachial artery at rest and during reactive hyperemia, and plasma endothelin-1 assays 3 months before and 6 weeks after the transplant. RESULTS: Office systolic and diastolic blood pressures increased significantly 6 weeks after liver transplantation (from 116.6+/-14.1 to 139.9+/-19.5 mmHg and from 68.6+/-9.5 to 84.1+/-9.8 mmHg, respectively; both P < 0.001). Hypertension based on office blood pressure readings increased from 6.7 to 40% (P < 0.05). Mean 24 h systolic blood pressure increased from 118.7+/-10.3 to 140.0+/-19.0 mmHg (P < 0.001), mean 24 h diastolic blood pressure increased from 86.0+/-7.7 to 104.8+/-13.9 mmHg (P < 0.001) and heart rate increased from 74.8+/-10.2 to 80.2+/-8.2 beats/min (P < 0.05). Brachial artery flow-mediated dilatation did not change throughout the study (before transplant: 4.2+/-4.0%; after transplant: 6.3+/-5.4%; NS) and did not differ from that in controls (5.2+/-3.8%). Plasma endothelin-1 was increased in patients with ESLD (15.3+/-2.6 pg/ml) compared with controls (5.6+/-0.4 pg/ ml; P < 0.001) and remained unchanged 6 weeks after liver transplantation (14.1+/-3.7 pg/ml). CONCLUSION: Our results show increased blood pressure with suppressed circadian blood pressure variability in liver graft recipients 6 weeks after transplant and no change in endothelial function and plasma endothelin concentrations. Therefore, the blood pressure increase documented in our study cannot be explained by endothelial dysfunction. Twenty-four hour ABPM should be performed routinely in patients who have undergone liver transplant.

The effect of renin and aldosterone inhibition by beta-adrenergic blockade on the response to the new diuretic azosemide.

The effect of repeated Azosemide infusions (20 mg in 500 ml 5% glucose for one h) on urine volume and electrolyte excretion, and on the activity of the renin-angiotensin-aldosterone system (RAAS) was studied in a group of 15 patients with benign essential hypertension before and during treatment with the beta-adrenergic blocker Trimepranol. Azosemide alone had a marked but short-lasting diuretic and natriuretic effect. Repeated administration on three consecutive days led, however, to a progressive decrease in the natriuretic effectiveness of Azosemide, associated with an increase in plasma renin activity (from 0.413 o.032 to 1.631 0.438 pmol/l). Treatment with Trimepranol 20 mg/day enhanced and prolonged the diuretic and natriuretic response to Azosemide concomitantly with a reduction of its stimulatory effect of RAAS. There results suggest that stimulation of the RAAS might be responsible for the diminishing effectiveness of repeated Azosemide infusions and that the stimulation could be, at least partly, inhibited by a beta-blocker Trimepranol, resulting in a greater diuretic and natriuretic effect of Azosemide.

Unilateral juxtaglomerular hyperplasia, hyperreninism and hypokalaemia relieved by nephrectomy.

Two women with spontaneous hypokalemia (1 normotensive, 1 hypertensive in the absence of renal artery stenosis), underwent unilateral nephrectomy because of angiographic and/or split renin-based suspicion of a reninoma. The normotensive patient clinically resembled Bartter syndrome but had some elements suggestive of a renin-secreting tumour, justifying surgical exploration and resection. The hypertensive patient presented clinically as a typical reninoma except for negative angiography. Surprisingly, the histology of the kidneys in both cases demonstrated juxtaglomerular hyperplasia without evidence of reninoma. The postoperative follow-up (8 and 19 yrs, respectively) has shown in the normotensive patient a considerable improvement in the hyper-reninism and previously uncontrollable hypokalaemia and in the hypertensive patient a complete normalisation of BP, renin and electrolyte status. Although the histological condition of the contralateral kidneys remains unknown in both patients the preoperative lateralisation of hyper-reninism to one kidney, the postoperative complete relief of the hyper-reninism in the hypertensive patient after uninephrectomy and its decrease, exceeding that corresponding to the removal of one kidney in the normotensive patient, suggest that the juxtaglomerular hyperplasia might have been unilateral or asymmetrical and that nephrectomy may, unexpectedly, relieve the hyper-reninism caused by juxtaglomerular hyperplasia. An increased unilateral susceptibility to trophic or renin-releasing factors or an asymmetrical abnormality in the macula densa-initiated mechanism of juxtaglomerular hyperplasia may be implicated in this disorder.

Metabolic, humoral and haemodynamic characteristics of normotensive offspring from hypertensive families.

Arterial hypertension is not only a haemodynamic abnormality, but it is associated with several metabolic and humoral changes. Heredity appears to be participating in the pathogenesis of essential hypertension (EH). We studied whether some metabolic, humoral and haemodynamic changes could be detected in genetically predisposed normotensive sons of hypertensive families (SH) compared with normotensive sons of normotensive parents (SN). The study groups consisted of 40 young SN and 40 SH matched for age and body mass index (BMI). Blood samples for laboratory determination were taken under basal conditions and 90 min after a 75 g glucose load. SH already had a higher systolic blood pressure (BP) (120.7 +/- 1.7 mm Hg) and a tendency to a higher diastolic BP than the SN group. In spite of the fact that both basal and stimulated glycemia did not differ significantly between the study groups, significantly higher glucose-stimulated immuno-reactive-insulin (IRI) was found in SH (80.1 +/- 7.06 vs 62.9 +/- 5.76 uU/l). Higher plasma concentration of catecholamines in SH indicate their higher sympathetico-adrenal activity. The groups did not differ significantly in basal and stimulated plasma renin activity (PRA), aldosterone and atrial natriuretic peptide (ANP). There was a tendency for higher levels of endothelin (ET) in the plasma of SH. The glucose load increased as expected, glycemia, IRI and C-peptide, but ANP and ET concentrations were unexpectedly reduced. These abnormalities were associated, in SH, with higher left ventricle (LV) mass index and impaired diastolic filling. Persistence of high LV mass index, even after adjustment for respective systolic BP, suggests the participation of more than haemodynamic stress in the increase of LV mass. Our results suggest that in normotensive genetically predisposed subjects from hypertensive families, some metabolic and humoral abnormalities can already be detected. They might be responsible for the higher BP readings with subsequent manifestations of hypertension and LV morphological and functional abnormalities.

Circulating intercellular cell adhesion molecule-1, endothelin-1 and von Willebrand factor-markers of endothelial dysfunction in uncomplicated essential hypertension: the effect of treatment with ACE inhibitors.

The aim of the study was to examine whether the circulating cell adhesion molecules, von Willebrand factor (vWf) and endothelin-1, are elevated in patients with essential hypertension with no other risk factors for atherosclerosis and thus may serve as a markers of endothelial dysfunction in uncomplicated hypertension. Furthermore, the effect of treatment with the ACE inhibitor, quinapril, on levels of endothelial dysfunction markers were studied. The levels of adhesion molecules (intercellular cell adhesion molecule-1 [ICAM-1], E-selectin, P-selectin), von Willebrand factor (vWf) and endothelin-1 were measured in patients with hypertension without any other risk factors of atherosclerosis before and after treatment with quinapril (n = 22) and in normotensive controls (n = 22). Compared with normotensive subjects, the hypertensive patients had significantly higher levels of ICAM-1 (238 vs 208 ng/ml, P = 0.02), vWf (119 vs 105 IU/dl, P < 0.05) and endothelin-1 (5.76 vs 5.14 fmol/ml, P < 0.05). Three-month treatment of hypertensive patients with quinapril led to a significant decrease in the levels of endothelin-1 (5.76 vs 5.28 fmol/ml, P < 0.01). We did not observe significant changes in the levels of adhesion molecules and vWf after ACE inhibitor treatment, although a trend toward a decrease was apparent with all these parameters. Patients with uncomplicated hypertension with no other risk factors of atherosclerosis had significantly elevated levels of ICAM-1, vWf, and endothelin-1. Our data suggest that these factors may serve as markers of endothelial damage even in uncomplicated hypertension. In hypertensive patients, treatment with the ACE inhibitor quinapril resulted in a significant decrease in endothelin-1 levels. These findings indicate a beneficial effect of ACE inhibitors on endothelial dysfunction in hypertensive patients.

Changes in proximal and distal coronary artery diameter during atrial pacing-induced myocardial ischemia.

BACKGROUND: The present study was designed to evaluate the role of tachycardia-induced dynamic coronary artery diameter changes in the development of myocardial ischemia. METHODS: Coronary angiography at rest and during atrial pacing-induced myocardial ischemia was performed in 22 patients. The diameter of the proximal and the corresponding distal coronary artery segments at rest and during pacing was measured using quantitative coronary angiography. Plasma levels of noradrenaline, adrenaline, dopamine and endothelin were determined in a subset of 14 patients in blood drawn from aorta and coronary sinus at rest and during pacing. RESULTS: Luminal diameter in normal proximal and distal segments increased, respectively, from 2.93 +/- 0.34 and 1.40 +/- 0.04 mm at rest to 3.03 +/- 0.25 and 1.58 +/- 0.07 mm during atrial pacing. The diameter of the proximal coronary artery segments with significant concentric stenosis decreased from 1.28 +/- 0.4 mm at rest to 0.95 +/- 0.34 mm during pacing, whereas segments with either significant eccentric or non-significant stenosis did not change significantly. A correlation was found between the noradrenaline level in the coronary sinus and the distal coronary artery diameter. CONCLUSIONS: A decrease in diameter of coronary artery segments with concentric stenosis during tachycardia might contribute to the development of myocardial ischemia. Some of the dynamic coronary artery changes may be influenced by the plasma level of noradrenaline. No evidence was found to suggest that dynamic changes in the diameter of proximal segments are related to the changes in diameter of the corresponding distal segments.

Development of a flow cytometric test for the detection of D-positive fetal cells after fetomaternal hemorrhage and a survey of the prevalence in D-negative women.

A sensitive test for the presence of D-positive fetal red blood cells (RBCs) in the maternal circulation of D-negative women has been developed. It was used to investigate the possibility that the occasional failure in preventing alloimmunization might be due to the administration of inadequate amounts of prophylactic anti-D Rh immune globulin. The standard dose in Australia contains 125 microg of antibody, and can suppress immunization by an estimated 6 mL of packed D-positive RBCs. A fetomaternal hemorrhage (FMH) of this volume is detectable in the maternal circulation as approximately 0.25 percent of the total RBCs. Our test utilizes a commercially available human monoclonal IgG anti-D that has been biotinylated and used with a dye-conjugated streptavidin. Flow cytometry is used to quantitate fluorescing D-positive RBCs. To date, 2,288 tests have been performed on blood samples from D-negative women attending local antenatal clinics or at the time of delivery. Evidence for an FMH has been obtained in six cases (0.26%). In one case, the FMH was only 0.1 percent, and in another (confirmed by the Kleihauer-Betke method), fetal cells constituted only 0.2 percent. Additional Rh immune globulin was not given to these patients. In the other four cases, the D-positive fetal cells were estimated to be 0.7,0.5,0.5, and 0.4 percent, and additional prophylactic Rh immune globulin was administered. Although the prevalence of FMH is low, screening D- negative women at risk of alloimmunization has proved to be simple, fast, and inexpensive.

[Endocrine function of the cardiovascular system]. / Endokrinní funkce kardiovaskulárního aparátu.

The cardiovascular system has in addition to it haemodynamic role also an important endocrine function. It produces a number of humoral substances which are either released into the circulation and exert a systemic endocrine effect (e.g. the atrial natriuretic factor from the atria) or act at the site of their genesis. This autocrine or paracrine action is typical above all for substances formed in the endothelium and vascular wall (endothelin, endothelium-derived relaxation factor, prostaglandins, prostacyclines, renin-angiotensin cascade etc.). Cardiovascular substances influence by their action markedly the general and organ haemodynamics, the volume and pressure homeostasis the development and regression, of cardiac hypertrophy and vascular walls, as well as thrombogenesis and atherogenesis. They participate thus in a significant way in physiological regulations and pathological processes in the organism.

[Hypertensive crisis and its treatment]. / Hypertenzní krize a moznosti její lécby.

Hypertensive crises threaten, due to the rapid rise of blood pressure the patient's life by cerebral, cardiovascular and renal complications. It may cause left-sided heart failure, dissection of the aorta, cerebral haemorrhage, renal failure. Patients with hypertensive crises are admitted to intensive care units with the possibility of systematic monitoring of the pulse rate, BP, ECG, diuresis and other vital functions. Treatment is started immediately by injections (usually i.v.) of antihypertensive drugs while monitoring the BP, vital functions and the general condition. At first small amounts of antihypertensives are administered and, depending on the BP, the dosage is adjusted. The recommended safe drop of BP which should be achieved within one hour is 100-110 mm Hg of diastolic BP or a 20% drop of the initial pressure. Concurrently with injections oral administration of antihypertensives is started. Correct treatment leads in the majority of patients to regression of hypertension and of acute danger to the patient's life. On the other hand, inadequate treatment threatens the patients with fatal complications.

[Renaissance of the renin-angiotensin system in the pathogenesis and therapy of arterial hypertension]. / Renesance systému renin-angiotensin v patogenezi a terapii arteriální hypertenze.

Favourable results with the use of inhibitors of the angiotension I-converting enzyme in the therapy not only of high-renin but also normo-renin and low-renin hypertension revived interest in research in the area of the renin-angiotensin (RAS) system. The use of classical radioimmunological, radiohistochemical receptor studies as well as of recent methods of molecular biology and pathology revealed that for the regulation of blood pressure and the extracellular volume and pathogenesis of hypertension not only RAS components in systemic blood are important but also local tissue RAS with an autocrine and paracrine action at the site of its origin. Cerebral RAS participates in the central cardiovascular regulation, in the control of the salt and water intake, the secretion of antidiuretic hormone and ACTH. In the cardiovascular apparatus RAS is responsible not only for vasoconstriction but it acts also as a growth factor promoting the development of cardiac and vascular hypertrophy. In the kidneys RAS decides on the blood flow, its distribution, glomerular filtration. Its excessive stimulation may contribute in arterial hypertension, diabetic nephropathy and in residual nephrons during chronic renal failure, to the change from functional hyperfiltration to irreversible structural damage of the nephron. Inhibitors of the converting enzyme not only reduce the peripheral vascular resistance in arterial hypertension but influence also the tissue production of angiotensin II and thus the regression of cardiovascular hypertrophy and progression of renal damage.

[Endothelin--a vasoactive peptide of endothelial cells]. / Endotelin--vazoaktivní peptid endotelových bunek.

Endothelin is a recently discovered peptide which is formed in the endothelial layer of the vascular wall and is released, following different stimuli, into the neighbouring smooth muscle layer of blood vessels and into the vascular lumen. By its effects on the regulation of the vascular tonus endothelin could play a part in regulating the function of various organ systems. The submitted paper gives a brief account on contemporary knowledge regarding the formation, elimination and biological effects of endothelin. The authors discuss also the potential physiological and pathophysiological role of this peptide.