Hyperinsulinaemia may play a causal role in the development of hypertension in obese hypertensives. However, experimental evidence supporting this statement is inappropriate. The main purpose of this study was to evaluate the chronic effects of insulin administration on blood pressure, total-body glucose metabolism and urinary catecholamine excretion. After 10 weeks of insulin injection blood pressure was substantially increased in insulin- treated animals compared to those treated with saline (125±2 vs 108±2 mm Hg, pcO.OOl). There were no differences in glycaemia, plasma triglyceride levels and free fatty acid levels between these two groups. Plasma level of corticosterone was increased in both insulin-treated and saline-treated rats as compared to untreated animals suggesting that the level of stress was similar in both injected groups. The urinary excretion of norepinephrine and dopamine was increased in the insulin-injected group by about 120 % and 310 %, respectively. Our data clearly indicate that long-term insulin administration increased blood pressure but the underlying mechanisms remain to be elucidated.
The agonists of α2-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 highrenin 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 a high-salt (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 IIdependent 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.
Transgenic mice overexpressing a transthyretin promoter-ANF structural fusion gene have a life-long reduction in arterial blood pressure compared to nontransgenic littermates. The present study was designed to test the hypothesis that the high plasma level of ANF in the transgenic mice inhibits the renin-angiotensin and/or vasopressin systems, thereby causing the hypotension. Mice were anaesthetized with Inactin and arterial pressure and heart rate were monitored before and during Saralasin infusion and vasopressin Vi receptor blockade. Effectiveness of the blockade was determined by injection of angiotensin and vasopressin before and during Saralasin and V] receptor antagonist administration. Saralasin was associated with hypotension in both transgenic and nontransgenic mice. The decrease in blood pressure was proportionally greater in the transgenic animals. Vasopressin receptor blockade had little effect on blood pressure in either group. Heart rates were not different between the groups during any maneuver. We conclude that the chronic hypotensive effect of ANF overproduction does not involve the inhibition of either renin-angiotensin or vasopressin systems. The data, however, suggest that the renin-angiotensin system may be stimulated in the ANF-transgenic mice.
Stress is considered a risk factor associated with the development of various civilization diseases including cardiovascular diseases, malignant tumors and mental disorders. Research investigating mechanisms involved in stress-induced hypertension have attracted much attention of physicians and researchers, however, there are still ambiguous results
concerning a causal relationship between stress and long-term
elevation of blood pressure (BP). Several studies have observed that mechanisms involved in the development of stress-induced hyperte
nsion include increased activity of sympathetic nervous system (SNS), glucocorticoid (GC) overload and altered endothelial functionincluding decreased nitric oxide (NO) bioavailability. Nitric oxide is well known neurotransmitter, neuromodulatorand vasodilator involved in regulation of
neuroendocrine mechanisms and cardiovascular responses to stressors. Thus NO plays a crucial role in the regulation of the stress systems and thereby in the BP regulation in stress. Elevated NO synthesis, especially in the initial phase of stress, may be considered a stress-limiting mechanism, facilitating the recovery from stress to the resting levels via attenuation of both GC release and SNS activity as well as by increased NO-dependent vasorelaxation. On the other hand, reduced levels of NO were observed in the later phases of stress and in subjects with genetic predisposition to hypertension, irrespectively, in which reduced NO bioavailability may account for disruption of NO-mediated BP regulatory mechanisms and accentuated SNS and GC effects. This review summarizes current knowledge on the role of stress in development of hypertension with a special focus on the interactions among NO and other biological systems
affecting blood pressure and vascular function.
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 poly tetrafluoroethylene (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., J. Chlupáč, E. Filová, L. Bačáková., and Obsahuje seznam literatury
Let $S^{\prime }$ be the class of tempered distributions. For $f\in S^{\prime }$ we denote by $J^{-\alpha }f$ the Bessel potential of $f$ of order $\alpha $. We prove that if $J^{-\alpha }f\in \mathop {\mathrm BMO}$, then for any $\lambda \in (0,1)$, $J^{-\alpha }(f)_\lambda \in \mathop {\mathrm BMO}$, where $(f)_\lambda =\lambda ^{-n}f(\phi (\lambda ^{-1}\cdot ))$, $\phi \in S$. Also, we give necessary and sufficient conditions in order that the Bessel potential of a tempered distribution of order $\alpha >0$ belongs to the $\mathop {\mathrm VMO}$ space.
Early mouse neural stem cells (NSCs) first appear in embryonic day E5.5 and express pluripotency markers Oct4, Sox2, Nanog and early neural marker Sox1. Early NSCs are a good model for understanding the role of various pathways that control initial neural commitment. However, a protocol for differentiation of mouse embryonic stem cells (ESCs) into early NSCs by adherent monolayer culture has not yet been established. Hence, in this study, we identified the combination of growth factors and small molecules that differentiated mouse ESCs into early NSCs and supported their proliferation. Leukaemia inhibitory factor (LIF) was the first factor to be tested and it was found that ESCs can differentiate into early neurogenic lineage in the presence of LIF. However, we found that the induction is weaker in the presence of LIF as compared to cells differentiated in its absence. GSK-3 inhibitor, along with BMP and TGF-β pathway inhibitor (dual SMAD inhibition), are commonly used to sequentially direct ESCs towards NSCs. However, when we used this combination, mouse ESCs failed to differentiate into early NSCs. We observed that by adding Wnt inhibitor to the combination of GSK-3 inhibitor, BMP inhibitor, TGF-β inhibitor and LIF, it was possible to differentiate ESCs into early NSCs. qRT-PCR analysis of early NSCs illustrated that they expressed key pluripotency genes Oct4 and Nanog, albeit at levels lower than non-differentiated ESCs, along with early neural markers Sox1 and Pax6.
Using the fluorescent differential display technique, a special band named Bm541 was identified by screening for differentially expressed genes in the resistant silkworm strain Qiufeng, the susceptible strain Huaba35, and the near isogenic line BC6, which carries the resistant gene to Bombyx mori densonucleosis virus (BmDNV). After applying the 5'RACE technique with specially designed primers, a 1148 bp cDNA clone containing a 387 bp open reading frame (ORF) was obtained. This gene was registered in GenBank under the accession number AY860950. The deduced amino acid sequence showed a 73.1% identity to the protein kinase C inhibitor (PKCI) of Drosophila pseudoobscura. In the deduced sequence of BmPKCI, the histidine triad (HIT) motif, which is essential for PKCI function, and the α-helix region, which is conserved among the PKCI family, were present. The data from quantitative real-time PCR (QRT-PCR) suggest that the expression levels of bmpkci in BC6 and Qiufeng both with BmDNV-Z are significantly higher than those in Huaba35, which indicate that BmPKCI plays a role in resistance to BmDNV-Z.