The pronounced activation of sympathetic nervous system is a necessary prerequisite for the development of neurogenic pulmonary edema (NPE) in rats with balloon compression of spinal cord. In this study we examined whether this is a consequence of rapid activation of spinal pathways leading to sympathetic venoconstriction, blood pressure rise, and reflex bradycardia. We found that NPE development can be prevented by epidural upper thoracic anesthesia or by transection of the upper spinal cord. This indicates an important role of spinal pathways activation. NPE development can also be prevented by moderate blood loss, supporting the role of blood redistribution to pulmonary circulation. In rats developing NPE the catecholamine surge following spinal cord compression involved not only a dramatic increase of circulating norepinephrine but also of epinephrine levels. The pretreatment of rats with α-1 adrenoceptor blocker prazosin, α-2 adrenoceptor blocker yohimbine, or calcium channel blocker nifedipine prevented NPE development, whereas the effect of β-adrenoceptor blockade with propranolol was less convincing. In conclusion, considerable activation of thoracic spinal pathways, followed by marked catecholamine secretion, play a major role in the development of NPE in spinal cord-injured rats. Enhanced α-adrenergic nifedipine-sensitive vasoconstriction is responsible for observed blood pressure changes, subsequent baroreflex bradycardia, and blood volume redistribution, which represent major pathogenetic mechanisms of NPE development.

• MeSH
• adrenalin krev   MeSH
• biologické markery krev   MeSH
• bradykardie krev   patofyziologie   MeSH
• hrudní obratle MeSH
• krevní tlak fyziologie   MeSH
• krysa rodu rattus MeSH
• noradrenalin krev   MeSH
• plicní edém krev   etiologie   patofyziologie   MeSH
• poranění míchy krev   komplikace   patofyziologie   MeSH
• potkani Wistar MeSH
• sympatický nervový systém fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Alterations in renal function contribute to Goldblatt two-kidney, one-clip (2K1C) hypertension. A previous study indicated that bioavailability of cytochrome P-450 metabolites epoxyeicosatrienoic acids (EETs) is decreased while that of 20-hydroxyeicosatetraenoic acids (20-HETE) is increased in this model. We utilized the inhibitor of soluble epoxide hydrolase cis-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (c-AUCB) and HET-0016, the inhibitor of 20-HETE production, to study the role of EETs and 20-HETE in the regulation of renal function. Chronic c-AUCB treatment significantly decreased systolic blood pressure (SBP) (133 ± 1 vs. 163 ± 3 mmHg) and increased sodium excretion (1.23 ± 0.10 vs. 0.59 ± 0.03 mmol/day) in 2K1C rats. HET-0016 did not affect SBP and sodium excretion. In acute experiments, renal blood flow (RBF) was decreased in 2K1C rats (5.0 ± 0.2 vs. 6.9 ± 0.2 ml·min(-1)·g(-1)). c-AUCB normalized RBF in 2K1C rats (6.5 ± 0.6 ml·min(-1)·g(-1)). HET-0016 also increased RBF in 2K1C rats (5.8 ± 0.2 ml·min(-1)·g(-1)). Although RBF and glomerular filtration rate (GFR) remained stable in normotensive rats during renal arterial pressure (RAP) reductions, both were significantly reduced at 100 mmHg RAP in 2K1C rats. c-AUCB did not improve autoregulation but increased RBF at all RAPs and shifted the pressure-natriuresis curve to the left. HET-0016-treated 2K1C rats exhibited impaired autoregulation of RBF and GFR. Our data indicate that c-AUCB displays antihypertensive properties in 2K1C hypertension that are mediated by an improvement of RBF and pressure natriuresis. While HET-0016 enhanced RBF, its anti-natriuretic effect likely prevented it from producing a blood pressure-lowering effect in the 2K1C model.

• MeSH
• amidiny farmakologie   MeSH
• epoxid hydrolasy antagonisté a inhibitory   MeSH
• inhibitory enzymů farmakologie   MeSH
• krevní tlak účinky léků   fyziologie   MeSH
• krysa rodu rattus MeSH
• kyseliny arachidonové metabolismus   MeSH
• kyseliny hydroxyeikosatetraenové metabolismus   MeSH
• ledviny krevní zásobení   účinky léků   fyziologie   MeSH
• modely nemocí na zvířatech MeSH
• regionální krevní průtok účinky léků   MeSH
• renovaskulární hypertenze metabolismus   patofyziologie   MeSH
• sodík moč   MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Essential hypertension is a major risk factor for several cardiovascular diseases. It is a complex trait resulting from the interactions of multiple genetic and environmental factors. Moreover, not only genetic but also epigenetic inheritance plays a significant role. One can speculate that hypertension develops as a consequence of "errors" in well-coordinated regulatory systems of blood pressure. Errors in the cascade of molecular, biochemical and genetic processes, which regulate blood pressure, have finally enough potential to result in hypertension. Numerous environmental factors surrounding the organism during its development should influence the expression of genetic information. However, despite the considerable research effort, it is still difficult to identify all genes and/or other genetic determinants leading to essential hypertension and other cardiovascular diseases. This is mainly because these diseases usually become a medical problem in adulthood, although their roots might be traced back to earlier stages of ontogeny. The link between distinct developmental periods (e.g. birth and adulthood) should involve changes in gene expression involving epigenetic phenomena. The purpose of the present paper is to bring a piece of light on gene-environmental interactions potentially implicated in the pathogenesis of hypertension.

• MeSH
• epigeneze genetická MeSH
• fenotyp MeSH
• financování organizované MeSH
• genetická predispozice k nemoci MeSH
• hypertenze genetika   patofyziologie   MeSH
• krevní tlak genetika   MeSH
• lidé MeSH
• rizikové faktory MeSH
• rodokmen MeSH
• věkové faktory MeSH
• životní prostředí MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Renin-angiotensin system (RAS) plays a key role in the regulation of renal function, volume of extracellular fluid and blood pressure. The activation of RAS also induces oxidative stress, particularly superoxide anion (O(2)(-)) formation. Although the involvement of O(2)(-) production in the pathology of many diseases is known for long, recent studies also strongly suggest its physiological regulatory function of many organs including the kidney. However, a marked accumulation of O(2)(-) in the kidney alters normal regulation of renal function and thus may contribute to the development of salt-sensitivity and hypertension. In the kidney, O(2)(-) acts as vasoconstrictor and enhances tubular sodium reabsorption. Nitric oxide (NO), another important radical that exhibits opposite effects than O(2)(-), is also involved in the regulation of kidney function. O(2)(-) rapidly interacts with NO and thus, when O(2)(-) production increases, it diminishes the bioavailability of NO leading to the impairment of organ function. As the activation of RAS, particularly the enhanced production of angiotensin II, can induce both O(2)(-) and NO generation, it has been suggested that physiological interactions of RAS, NO and O(2)(-) provide a coordinated regulation of kidney function. The imbalance of these interactions is critically linked to the pathophysiology of salt-sensitivity and hypertension.

• MeSH
• angiotensin II metabolismus   MeSH
• financování organizované MeSH
• hypertenze etiologie   metabolismus   patofyziologie   MeSH
• krevní tlak MeSH
• kuchyňská sůl škodlivé účinky   MeSH
• ledviny metabolismus   patofyziologie   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• oxid dusnatý metabolismus   MeSH
• oxidační stres MeSH
• renin-angiotensin systém MeSH
• sodík metabolismus   MeSH
• superoxidy metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• přehledy MeSH

Renin-angiotensin system (RAS) plays a key role in the regulation of renal function, volume of extracellular fluid and blood pressure. The activation of RAS also induces oxidative stress, particularly superoxide anion (O(2)(-)) formation. Although the involvement of O(2)(-) production in the pathology of many diseases is known for long, recent studies also strongly suggest its physiological regulatory function of many organs including the kidney. However, a marked accumulation of O(2)(-) in the kidney alters normal regulation of renal function and thus may contribute to the development of salt-sensitivity and hypertension. In the kidney, O(2)(-) acts as vasoconstrictor and enhances tubular sodium reabsorption. Nitric oxide (NO), another important radical that exhibits opposite effects than O(2)(-), is also involved in the regulation of kidney function. O(2)(-) rapidly interacts with NO and thus, when O(2)(-) production increases, it diminishes the bioavailability of NO leading to the impairment of organ function. As the activation of RAS, particularly the enhanced production of angiotensin II, can induce both O(2)(-) and NO generation, it has been suggested that physiological interactions of RAS, NO and O(2)(-) provide a coordinated regulation of kidney function. The imbalance of these interactions is critically linked to the pathophysiology of salt-sensitivity and hypertension.

• MeSH
• angiotensin II metabolismus   MeSH
• financování organizované MeSH
• hypertenze etiologie   metabolismus   patofyziologie   MeSH
• krevní tlak MeSH
• kuchyňská sůl škodlivé účinky   MeSH
• ledviny metabolismus   patofyziologie   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• oxid dusnatý metabolismus   MeSH
• oxidační stres MeSH
• renin-angiotensin systém MeSH
• sodík metabolismus   MeSH
• superoxidy metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• přehledy MeSH

Prague hereditary hypercholesterolemic (PHHC) rat - rat strain crossbred from Wistar rats - is a model of hypercholesterolemia induced by dietary cholesterol. Importantly, no bile salts and/or antithyroid drugs need to be added to the diet together with cholesterol to induce hypercholesterolemia. PHHC rats have only modestly increased cholesterolemia when fed a standard chow and develop hypercholesterolemia exceeding 5 mmol/l on 2 % cholesterol diet. Most of the cholesterol in hypercholesterolemic PHHC rats is found in VLDL that become enriched with cholesterol (VLDL-C/VLDL-TG ratio > 1.0). Concurrently, both IDL and LDL concentrations rise without any increase in HDL. PHHC rats do not markedly differ from Wistar rats in the activities of enzymes involved in intravascular remodelation of lipoproteins (lipoprotein and hepatic lipases and lecithin:cholesterol acyltransferase), LDL catabolism, cholesterol turnover rate and absorption of dietary cholesterol. The feeding rats with cholesterol diet results in development of fatty liver in spite of suppression of cholesterol synthesis. However, even though cholesterolemia in PHHC rats is comparable to human hypercholesterolemia, the PHHC rats do not develop atherosclerosis even after 6 months on 2 % cholesterol diet. Importantly, the crossbreeding experiments documented that hypercholesterolemia of PHHC rats is polygenic. To identify the genes that may be involved in pathogenesis of hypercholesterolemia in this strain, the studies of microarray gene expression in the liver of PHHC rats are currently in progress.

• MeSH
• ateroskleróza genetika   metabolismus   patologie   MeSH
• cholesterol dietní škodlivé účinky   MeSH
• cholesterol krev   MeSH
• fenotyp MeSH
• financování organizované MeSH
• genetická predispozice k nemoci MeSH
• hybridizace genetická MeSH
• hypercholesterolemie genetika   krev   patologie   MeSH
• játra metabolismus   patologie   MeSH
• krysa rodu rattus MeSH
• lipoproteiny krev   MeSH
• modely nemocí na zvířatech MeSH
• multifaktoriální dědičnost MeSH
• potkani Wistar MeSH
• progrese nemoci MeSH
• ztučnělá játra genetika   metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• přehledy MeSH

High plasma levels of triglycerides (TG) are an independent risk factor in the development of cardiovascular disease, with about 50 % of the final levels being determined genetically. Apolipoprotein A5 (APOA5) is the last discovered member of the apolipoprotein APOA1/C3/A4 gene cluster, found by comparative sequencing analysis. The importance of APOA5 gene for determination of plasma triglyceride levels has been suggested after development of transgenic and knock-out mice (transgenic mice displayed significantly reduced TG, whereas knock-out mice had high TG). In Czech population, alleles C-1131 and Trp19 are associated with elevated levels of plasma TG and higher risk of myocardial infarction development. These alleles also play some role in nutrigenetics and actigenetics of lifestyle interventions leading to the plasma cholesterol changes as well as in the pharmacogenetics of statin treatment. On the contrary, APOA5 mutations detected in Czech population did not show strict effect on plasma TG levels. Val153 --> Met variant exhibit the sex-specific effect of HDL-cholesterol levels. The suggested roles of APOA5 variants in determination of the plasma remnant particles, plasma concentrations of C-reactive protein or some anthropometrical parameters were excluded.

• MeSH
• apolipoproteiny A genetika   krev   MeSH
• apolipoproteiny genetika   MeSH
• fenotyp MeSH
• financování organizované MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• hodnocení rizik MeSH
• hypercholesterolemie genetika   krev   MeSH
• infarkt myokardu genetika   krev   prevence a kontrola   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myši knockoutované MeSH
• myši MeSH
• polymorfismus genetický MeSH
• triglyceridy krev   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• přehledy MeSH

The gold standard material in bypass surgery of blood vessels remains the patient's own artery or vein. However, this material may be unavailable, or may suffer vein graft disease. Currently available vascular prostheses, namely polyethylene terephthalate (PET, Dacron) and expanded polytetrafluoroethylene (ePTFE), perform well as large-caliber replacements, but their long-term patency is discouraging in small-caliber applications (<6 mm), such as in coronary, crural or microvessel surgery. This failure is mainly a result of an unfavorable healing process with surface thrombogenicity, due to lack of endothelial cells and anastomotic intimal hyperplasia caused by hemodynamic disturbances. An ideal small-diameter vascular graft has become a major focus of research. Novel biomaterials have been manufactured, and tissue-biomaterial interactions have been optimized. Tissue engineering technology has proven that the concept of partially or totally living blood vessels is feasible. The purpose of this review is to outline the vascular graft materials that are currently being implanted, taking into account cell-biomaterial physiology, tissue engineering approaches and the collective achievements of the authors.

• MeSH
• biokompatibilní materiály MeSH
• bioprotézy dějiny   trendy   MeSH
• časové faktory MeSH
• cévní protézy dějiny   trendy   MeSH
• cévy - implantace protéz MeSH
• dějiny 20. století MeSH
• dějiny 21. století MeSH
• financování organizované MeSH
• lidé MeSH
• nemoci cév chirurgie   patofyziologie   MeSH
• okluze cévního štěpu etiologie   prevence a kontrola   MeSH
• protézy - design MeSH
• průchodnost cév MeSH
• tkáňové inženýrství dějiny   trendy   MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• dějiny 20. století MeSH
• dějiny 21. století MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• přehledy MeSH

Blood pressure (BP) level results from the balance of vasoconstrictors (mainly sympathetic nervous system) and vasodilators (predominantly nitric oxide and endothelium-derived hyperpolarizing factor). Most of the forms of experimental hypertension are associated with sympathetic hyperactivity and endothelial dysfunction. It is evident that nitric oxide and norepinephrine are antagonists in the control of calcium influx through L-type voltage-dependent calcium channels (L-VDCC). Their effects on L-VDCC are mediated by cGMP and cAMP, respectively. Nevertheless, it remains to determine whether these cyclic nucleotides have direct effects on L-VDCC or they act through a modulation of calcium-activated K(+) and Cl(-) channels which influence membrane potential. Rats with genetic or salt hypertension are characterized by a relative (but not absolute) NO deficiency compared to the absolute enhancement of sympathetic vasoconstriction. This dysbalance of vasoconstrictor and vasodilator systems in hypertensive animals is reflected by greater calcium influx through L-VDCC susceptible to the inhibition by nifedipine. However, when the modulatory influence of cyclic nucleotides is largely attenuated by simultaneous ganglionic blockade and NO synthase inhibition, BP of spontaneously hypertensive rats remains still elevated compared to normotensive rats due to augmented nifedipine-sensitive BP component. It remains to determine why calcium influx through L-VDCC of hypertensive rats is augmented even in the absence of modulatory influence of major vasoactive systems (sympathetic nervous system, nitric oxide).

• MeSH
• alfa-adrenergní receptory metabolismus   MeSH
• chloridové kanály metabolismus   MeSH
• financování organizované MeSH
• gating iontového kanálu MeSH
• genetická predispozice k nemoci MeSH
• hypertenze etiologie   metabolismus   patofyziologie   MeSH
• krevní tlak MeSH
• krysa rodu rattus MeSH
• kuchyňská sůl škodlivé účinky   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• nukleotidy cyklické metabolismus   MeSH
• oxid dusnatý metabolismus   MeSH
• potkani inbrední SHR MeSH
• proteiny vázající GTP - alfa-podjednotky Gi-Go metabolismus   MeSH
• sympatický nervový systém patofyziologie   MeSH
• vápník metabolismus   MeSH
• vápníková signalizace MeSH
• vápníkové kanály - typ L metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• přehledy MeSH

Important fetal and perinatal pathologies, especially intrauterine growth restriction (IUGR), are thought to stem from placental hypoxia-induced vasoconstriction of the fetoplacental vessels, leading to placental hypoperfusion and thus fetal undernutrition. However, the effects of hypoxia on the fetoplacental vessels have been surprisingly little studied. We review here available experimental data on acute hypoxic fetoplacental vasoconstriction (HFPV) and on chronic hypoxic elevation of fetoplacental vascular resistance. The mechanism of HFPV includes hypoxic inhibition of potassium channels in the plasma membrane of fetoplacental vascular smooth muscle and consequent membrane depolarization that activates voltage gated calcium channels. This in turn causes calcium influx and contractile apparatus activation. The mechanism of chronic hypoxic elevation of fetoplacental vascular resistance is virtually unknown except of signs of the involvement of morphological remodeling.

• MeSH
• akutní nemoc MeSH
• cévní rezistence MeSH
• chronická nemoc MeSH
• financování organizované MeSH
• hemodynamika MeSH
• hypoxie plodu komplikace   metabolismus   patofyziologie   MeSH
• iontové kanály metabolismus   MeSH
• lidé MeSH
• placentární oběh MeSH
• růstová retardace plodu etiologie   patofyziologie   MeSH
• signální transdukce MeSH
• svaly hladké cévní metabolismus   patofyziologie   MeSH
• těhotenství MeSH
• vazokonstrikce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• přehledy MeSH