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Some aspects of pathophysiology of pulmonary arterial hypertension and its epidemiology in the Czech Republic
Jansa, Pavel ; Aschermann, Michael (advisor) ; Widimský, Jiří (referee) ; Čerbák, Roman (referee)
1 Univerzita Karlova v Praze 1. lékařská fakulta Některé aspekty patofyziologie plicní arteriální hypertenze a její výskyt v České republice Some aspects of pathophysiology of pulmonary arterial hypertension and its epidemiology in the Czech Republic MUDr. Pavel Jansa Praha 2011 2 Abstract Pulmonary arterial hypertension (PAH) is a group of diseases characterized by a progressive increase of resistance and pressure in pulmonary vascular bed. In all types of PAH the same four pathological processes are reported: vasoconstriction, inflammation, thrombosis and remodelling. The genetic background is essential for the development of PAH. We aimed to investigate the role of polymorphisms of endothelial nitric oxide synthase (eNOS) genes in PAH. We studied 142 PAH patients and 189 healthy subjects. We examined 3 polymorphisms of the eNOS gene, including the Glu298Asp polymorphism, 27-base pair (bp) variable numbers of tandem repeats (VNTR) and -786 T/C promoter gene polymorphism. Prevalence of 27-bp VNTR allele A was higher in patients with PAH compared with healthy controls. Patients with PAH associated with connective tissue diseases had higher prevalence of AA genotype compared with other PAH subgroups. The Glu298Asp polymorphism and -786 T/C polymorphism are not associated with PAH. Thrombotic arteriopathy is...
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Large artery properties in primary and secondary - endocrine hypertension
Rosa, Ján ; Widimský, Jiří (advisor) ; Mlíková Seidlerová, Jitka (referee) ; Špinar, Jindřich (referee)
Arterial stiffness represented by carotid-femoral pulse wave velocity (PWV) is considered to be an independent cardiovascular risk factor. This study was focused on large artery properties investigation in specific forms of hypertension using applanation tonometer Sphygmocor (Atcor Medical). PWV was significantly higher in resistant hypertension patients when compared to moderate essential hypertension (EH) patients. This difference appears to be independent of clinical blood pressure (BP). Night-time BP appears to be a more accurate predictor of PWV in EH. In another study we demonstrated that primary hyperparathyroidism (PH) (both hypertensive or non-hypertensive forms) might be associated with higher PWV when compared to EH patients or to normotensive controls and that this difference is independent of age and clinical BP. Neither calcium serum level, nor parathyroid hormone has been associated with PWV. Specific treatment by parathyroidectomy (PTX) seems to be beneficial for PWV decrease, which might be mainly determined by improved BP control after surgery. Since PTX indications for asymptomatic forms of PH have been discussed, our data suggest the potential benefit to the extent of subclinical organ damage after surgical treatment in these patients. Similarly, we prooved higher PWV in...
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Alteration of cardiovascular system in endocrine hypertension, diagnostic and therapeutic aspects
Petrák, Ondřej ; Widimský, Jiří (advisor) ; Kittnar, Otomar (referee) ; Filipovský, Jan (referee)
aj This study contributes to knowledge of pathophysiology and organ complication in endocrine hypertension, especially in primary hyperaldosteronism and pheochromocytoma. Study in patients with pheochromocytoma showed higher arterial stiffness due to catecholamine overproduction. In this study we pointed out that predominantly norepinephrine levels and concomitant high blood glucose levels were independently associated with arterial stiffness. Similarly, a study in patients with primary hyperaldosteronism showed higher arterial stiffness in comparison with a comparable group of essential hypertension. This finding should be one of the factors which contribute to higher cardiovascular morbidity and mortality in patients with primary hyperaldosteronism. A study of biochemical markers of endothelial dysfunction has still showed contradictory conclusions. The position of the markers in clinical practice has not been resolved yet. In our study, we did not reveal any convincing evidence of differences in the levels of biochemical markers of endothelial dysfunction between the essential and endocrine hypertensions. The contemporary accepted marker of endothelial dysfunction and atherosclerosis is C-reactive protein as a marker of a chronic low inflammation process. Our study in patients with...
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The role of the endothelin system in development of hypertension and hypertensive end-organ damage in Ren-2 transgenic rats
Opočenský, Martin ; Červenka, Luděk (advisor) ; Neckář, Jan (referee) ; Widimský, Jiří (referee)
The role of the endothelin system in development of hypertension and hypertensive end- organ damage in Ren-2 transgenic rats Endothelin-I (ET-I) has been described as one ofthe most powerful vasoconstrictors, that also play a role in the regulation of renal hemodynamics. ET system plays an important role in the pathogenesis of salt-sensitive models of hl'pertension. The benefícial effects of ET receptor blockers in modulating target-organ damage arise rrom their antiproliferative action. There is, however, a large discrepancy in the effect of ET between various models of hypertension. The hypertensive rat strain transgenic for the mouse Ren-2 (TGR) renin gene is a valuable monogenetic model of renin-dependent and thus angiotensin lI(Ang ll) - dependent hypertension, which exhibits typical signs of fulminant hypertension,i.e. reduced glomerular fíltration rate and proteinuria associated with g1omerulosderosis. Moreover, it carries a salt- sensitive component. We have recently found that nonselective endothelin ETA/ETB receptor blockade markedly improves survival rate and ameliorates end'-organ damage in malcTGR without lowering blood pressure. Because activation ofthe ETA receptor may be responsible for the detrimental effects of ET in the development of hypertension, our study was performed to...
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Interactive Influence of Genetic Effects and Effects of External Environment on Properties of Large Arteries in Relation to Sodium Management
Seidlerová, Jitka ; Filipovský, Jan (advisor) ; Widimský, Jiří (referee) ; Segers, Patrick (referee) ; Herijgers, Paul (referee)
In line with Guyton's work, the goal of our research was to explore in three European populations whether the properties of large arteries are associated with renal sodium handling, which itself changes with environmental factors and with variation in a large number of genes. Before engaging in the genetic analyses proper, we first studied the familial aggregation and the heritability of arterial properties. In all our analyses, we accounted for relatedness among participants and for covariables and confounders. In a first study, we compared the arterial characteristics and blood pressure (BP) in normotensive offspring of two normotensive parents (OFF/NT) and normotensive offspring, who had at least one hypertensive parent (OFF/HT). We measured peripheral pulse pressure (PPp) by conventional and 24-h ambulatory BP. A SphygmoCor device was used to determine the central (CAIx) and peripheral (PAIx) augmentation indexes, central pulse pressure (PPc), and aortic pulse wave velocity (aPWV). Compared with OFF/NT (n=59; 16 to 34 years of age), the OFF/HT (n=174; 17 to 40 years) had higher (0.14<P<0.0007) BP and PPp on conventional measurement (121/75 vs. 114/71 mm Hg and 46 vs. 42 mm Hg) as well as on 24-h ambulatory monitoring (118/70 vs. 114/67 mm Hg and 48 vs. 47 mm Hg). OFF/HT, compared with OFF/NT, also had...
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