Sympathetic hyperactivity and relative NO deficiency are characteristic alterations in both genetic and salt hypertension. The contribution of these abnormalities to blood pressure (BP) maintenance can be determined in conscious rats using a consecutive blockade of particular vasoactive systems. Thus, the contribution of pressor effects of angiotensin II to the maintenance of high BP is usually small, but the role of renin-angiotensin system in the development of hypertension mediated by central and peripheral effects of angiotensin II on sympathetic activity is highly important. This is even true in angiotensin-dependent hypertension of heterozygous Ren-2 transgenic rats in which sympathetic hyperactivity is increasing with age. Central sympathoexcitation in this hypertensive model can be inhibited by lower losartan doses than peripheral angiotensin II-dependent vasoconstriction. This experimental model also yielded important knowledge on nephroprotective effects of new therapeutic drugs - endothelin receptor type A blockers. A considerable part of sympathetic vasoconstriction is dependent on the interaction of Ca2+ sensitization (RhoA/Rho kinase pathway) and Ca2+ influx (through L-VDCC). The blockade of these pathways prevents a major part of sympathetic vasoconstriction. Ca2+ sensitization seems to be attenuated in genetic hypertension in order to compensate increased Ca2+ influx. In contrast, enhanced Ca2+ sensitization is a hallmark of salt sensitivity in Dahl rats in which salt hypertension is dependent on increased Ca2+ influx. The attention should also be paid to the impairment of arterial baroreflex sensitivity which permits enhanced BP responses to pressor or depressor stimuli. Some abnormalities can be studied in blood vessels isolated from hypertensive rats but neither conduit arteries nor mesenteric resistance arteries represent the vascular beds decisive for the increased peripheral resistance and high BP. Keywords: Sympathetic vasoconstriction, NO-dependent vasodilatation, Calcium sensitization, Calcium influx, Arterial baroreflex, Spontaneously hypertensive rats, Salt hypertensive Dahl rats, Ren-2 transgenic rats, RAS blockade, SNS blockade, NOS inhibition, Endothelin, Vascular contraction and relaxation, Isolated conduit and resistance arteries, EDCF, PGI2, BKCa channels.

• MeSH
• Hypertension * physiopathology   metabolism   MeSH
• Blood Pressure drug effects   physiology   MeSH
• Rats MeSH
• Humans MeSH
• Disease Models, Animal MeSH
• Renin-Angiotensin System drug effects   physiology   MeSH
• Sympathetic Nervous System physiopathology   drug effects   MeSH
• Vasodilation drug effects   physiology   MeSH
• Vasoconstriction * drug effects   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Inducible NO synthase (NOS II) was proposed to play an important role in salt resistance of Dahl salt-resistant (SR/Jr) rats. Its chronic inhibition by specific inhibitors was accompanied by blood pressure (BP) elevation in animals subjected to high salt intake. The aim of our study was to evaluate 1) whether such inhibitors affect BP and/or its particular components (sympathetic tone and NO-dependent vasodilation) only under the conditions of high salt intake, and 2) whether similar BP effects are elicited after systemic or intracerebroventricular (icv) application of these inhibitors. Wistar rats fed Altromin diet (0.45 % NaCl) and SR/Jr rats fed either a low-salt (LS, 0.3 % NaCl) or a high-salt (HS, 4 % NaCl) diet were studied. Aminoguanidine (AMG) and 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT) were used as NOS II inhibitors. BP and its responses to acute blockade of renin-angiotensin system (captopril), sympathetic nervous system (pentolinium) and NO synthase (L-NAME) were measured in conscious cannulated rats. There were no significant changes of BP or its components in either Wistar rats or SR/Jr rats subjected to chronic inhibition of NOS II by peroral aminoguanidine administration (50 mg/kg/day for 4 weeks). This was true for SR/Jr rats fed either LS or HS diets. Furthermore, we have studied BP effects of chronic icv administration of both NOS II inhibitors in SR/Jr rats fed HS diet, but we failed to find any BP changes elicited by such treatment. In conclusion, inducible NO synthase does not participate in the resistance of SR/Jr rats to hypertensive effects of excess salt intake.

• MeSH
• Sodium Chloride MeSH
• Hypertension * chemically induced   MeSH
• Blood Pressure physiology   MeSH
• Rats MeSH
• Sodium Chloride, Dietary * MeSH
• Nitric Oxide MeSH
• Rats, Inbred Dahl MeSH
• Rats, Wistar MeSH
• Nitric Oxide Synthase Type II MeSH
• Nitric Oxide Synthase MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

• Publication type
• Meeting Abstract MeSH

Učebnice angličtiny, která se zaměřuje na nutriční terapii. Určeno odborníkům v praxi.

• Keywords
• angličtina,
• MeSH
• Nutrition Therapy MeSH
• Publication type
• Textbook MeSH

• Conspectus
• Fyzioterapie. Psychoterapie. Alternativní lékařství
• Lingvistika. Jazyky
• Učební osnovy. Vyučovací předměty. Učebnice
• NML Fields
• nutriční terapie, dietoterapie a výživa
• lingvistika, lékařská terminologie

The agonists of alpha(2)-adrenergic receptors such as clonidine, rilmenidine or monoxidine are known to lower blood pressure (BP) through a reduction of brain sympathetic outflow but their chronic antihypertensive effects in rats with low-renin or high-renin forms of experimental hypertension were not studied yet. Moreover, there is no comparison of mechanisms underlying BP reduction elicited by chronic peroral (po) or intracerebroventricular (icv) clonidine treatment. Male salt-sensitive Dahl rats fed 4% NaCl diet and Ren-2 transgenic rats were treated with clonidine administered either in the drinking fluid (0.5 mg/kg/day po) or as the infusion into lateral brain ventricle (0.1 mg/kg/day icv) for 4 weeks. Basal BP and the contributions of renin-angiotensin system (captopril 10 mg/kg iv) or sympathetic nervous system (pentolinium 5 mg/kg iv) to BP maintenance were determined in conscious cannulated rats at the end of the study. Both peroral and intracerebroventricular clonidine treatment lowered BP to the same extent in either rat model. However, in both models chronic clonidine treatment reduced sympathetic BP component only in rats treated intracerebroventricularly but not in perorally treated animals. In contrast, peroral clonidine treatment reduced angiotensin II-dependent vasoconstriction in Ren-2 transgenic rats, whereas it lowered residual blood pressure in Dahl rats. In conclusions, our results indicate different mechanisms of antihypertensive action of clonidine when administered centrally or systemically.

• MeSH
• Angiotensin II pharmacology   MeSH
• Antihypertensive Agents pharmacology   MeSH
• Sodium Chloride MeSH
• Clonidine pharmacology   MeSH
• Hypertension * chemically induced   drug therapy   MeSH
• Hypotension * MeSH
• Blood Pressure MeSH
• Rats MeSH
• Sodium Chloride, Dietary MeSH
• Rats, Inbred Dahl MeSH
• Rats, Transgenic MeSH
• Renin MeSH
• Sympathetic Nervous System MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Oblast nekomerčních klinických studií zaznamenává v posledních letech významný vzestup hlavně v kontextu precision medicine a individualizované léčby. Nekomerční studie totiž poskytují prostor pro výzkum otázek přiléhavějších klinické praxi a nabízí příležitost pro využití inovativních designů klinických studií. Nekomerční klinické studie ale současně kladou vyšší nároky na hlavní zkoušející a členy jejich týmů, neboť tito svou pozici ve studii rozšiřují o koordinační a manažerskou roli zadavatele. Na druhé straně je vzdělávání v oblasti organizace a teorie klinických studií na lékařských a farmaceutických fakultách v České republice poměrně skromné. Typicky je zařazeno do výuky farmakologie jako součást přiblížení celého procesu výzkumu a vývoje léčiva. V postgraduálním stupni jsou pak pouze na některých fakultách otevírány komplexní předměty věnující se organizaci a interpretaci klinických studií. Projekty ERASMUS+ CONSCIOUS a ERASMUS+ CONSCIOUS II tak mohou pomoci zaplnit mezeru ve vzdělávání v této oblasti, nabízí totiž ucelený, bezplatně přístupný soubor lekcí pro pregraduální a postgraduální studenty biomedicínských oborů a plánována je také otevřená pilotní výuka formou dvanácti on-line lekcí s mezinárodní účastí.

The field of non-commercial clinical trials has experienced significant expansion in recent years, especially in the context of precision medicine and individualized treatment. Indeed, non-commercial trials provide a venue for research on questions relevant to clinical practice and offer the opportunity to use innovative clinical trial designs. At the same time, however, non-commercial clinical trials place greater demands on principal investigators and their team members as they extend their position in the study to include the coordination and management role of the sponsor. On the other hand, training in the organization and theory of clinical trials at medical and pharmaceutical faculties in the Czech Republic is limited. It is typically included in pharmacology as part of an introduction to the overall process of drug research and development. At the postgraduate level, only some faculties offer comprehensive courses on the organization and interpretation of clinical trials. The ERASMUS+ CONSCIOUS and ERASMUS+ CONSCIOUS II projects can thus help to fill the gap in education in this area, offering a comprehensive, free-of-charge collection of lessons for undergraduate and postgraduate biomedical students, and an open pilot course of twelve on-line lessons with international participation is also planned.

• Keywords
• CONSCIOUS II,
• MeSH
• Clinical Trials as Topic * MeSH
• Humans MeSH
• Professional Competence MeSH
• Education, Medical * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

Sedace je jedním z nejčastějších terapeutických opatření na jednotkách intenzivní péče. Aktuálním trendem je snaha o její minimalizaci a pravidelné sledování úrovně sedace za pomoci validovaných skórovacích systémů. Monitorace hloubky anestezie a sedace, založená na analýze EEG, je již delší dobu používaná v anesteziologii. Druhý díl přehledového článku se zabývá vývojem této technologie a její přenositelností do prostředí intenzivní medicíny.

Pharmacological sedation is one of the most common therapies in the intensive care unit (ICU). Current approach is minimalization of sedation and frequent monitoring of its level, using validated sedation scales. The depth of the anaesthesia and sedation monitoring based on the automated EEG analysis is used in anaesthesiology for more than two decades. The second part of the review is focused on the development of this technology and its possible application in the ICU.

• MeSH
• Analgesia * MeSH
• Conscious Sedation MeSH
• Electroencephalography methods   MeSH
• Humans MeSH
• Drug Monitoring methods   MeSH
• Critical Care methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

It is generally accepted that angiotensin II plays an important role in high blood pressure (BP) development in both 2-kidney-1-clip (2K1C) Goldblatt hypertension and in partial nephrectomy (NX) model of chronic kidney disease (CKD). The contribution of sympathetic nervous system and nitric oxide to BP control in these models is less clear. Partial nephrectomy or stenosis of the renal artery was performed in adult (10-week-old) male hypertensive heterozygous Ren-2 transgenic rats (TGR) and normotensive control Hannover Sprague Dawley (HanSD) rats and in Wistar rats. One and four weeks after the surgery, basal blood pressure (BP) and acute BP responses to the consecutive blockade of renin-angiotensin (RAS), sympathetic nervous (SNS), and nitric oxide (NO) systems were determined in conscious rats. Both surgical procedures increased plasma urea, a marker of renal damage; the effect being more pronounced following partial nephrectomy in hypertensive TGR than in normotensive HanSD rats with a substantially smaller effect in Wistar rats after renal artery stenosis. We demonstrated that the renin-angiotensin system does not play so fundamental role in blood pressure maintenance during hypertension development in either CKD model. By contrast, a more important role is exerted by the sympathetic nervous system, the activity of which is increased in hypertensive TGR-NX in the developmental phase of hypertension, while in HanSD-NX or Wistar-2K1C it is postponed to the established phase. The contribution of the vasoconstrictor systems (RAS and SNS) was increased following hypertension induction. The role of NO-dependent vasodilation was unchanged in 5/6 NX HanSD and in 2K1C Wistar rats, while it gradually decreased in 5/6 NX TGR rats.

• MeSH
• Renal Insufficiency, Chronic complications   metabolism   physiopathology   MeSH
• Hypertension complications   metabolism   physiopathology   MeSH
• Blood Pressure physiology   MeSH
• Rats MeSH
• Disease Models, Animal MeSH
• Rats, Sprague-Dawley MeSH
• Rats, Transgenic MeSH
• Rats, Wistar MeSH
• Renin-Angiotensin System * MeSH
• Sympathetic Nervous System physiopathology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

• MeSH
• Conscious Sedation adverse effects   MeSH
• Antihypertensive Agents * administration & dosage   adverse effects   therapeutic use   MeSH
• Adrenergic beta-Antagonists administration & dosage   adverse effects   therapeutic use   MeSH
• Calcium Channel Blockers administration & dosage   adverse effects   therapeutic use   MeSH
• Angiotensin II Type 1 Receptor Blockers administration & dosage   adverse effects   therapeutic use   MeSH
• Diuretics administration & dosage   adverse effects   therapeutic use   MeSH
• Edema chemically induced   complications   prevention & control   MeSH
• Hypokalemia complications   prevention & control   MeSH
• Angiotensin-Converting Enzyme Inhibitors administration & dosage   adverse effects   therapeutic use   MeSH
• Cough chemically induced   complications   prevention & control   MeSH
• Humans MeSH
• Meta-Analysis as Topic MeSH
• Drug-Related Side Effects and Adverse Reactions * drug therapy   complications   prevention & control   MeSH
• Hypotension, Orthostatic chemically induced   complications   prevention & control   MeSH
• Arrhythmias, Cardiac chemically induced   complications   prevention & control   MeSH
• Statistics as Topic MeSH
• Patient Dropouts * MeSH
• Check Tag
• Humans MeSH