Epidemiological and clinical studies suggest that asthma is associated with adverse cardiovascular outcomes, but its mechanism is uncertain. 5-Hydroxytryptamine (5-HT) is a mediator involved in asthma and in cardiovascular functioning. Thus, in the present study, we explored whether allergic sensitization in guinea pigs modifies 5-HT-induced contractile responses and 5-HT2A receptor expression in thoracic aorta rings. We found that sensitization produced a significant increase of 100 microM 5-HT-induced contractions of aorta rings (~27 % greater contraction than in non-sensitized animals, p<0.05). Preincubation with 10 nM ketanserin (a 5-HT2A receptor antagonist) reduced by ~30 % (p=0.003) and ~36 % (p=0.005) the area under the curve of 5-HT-induced contractions in aortas from non-sensitized and sensitized animals, respectively. There were no differences between sensitized and non-sensitized animals with respect to mRNA (qPCR) and protein (Western blot) expression of 5-HT2A receptor in thoracic aortas. We concluded that in this guinea pig model of asthma, allergic sensitization is not confined to airways, but also affects arterial contractile responses to 5-HT; changes in the expression of the 5-HT2A receptor appear not to be involved in this phenomenon.
- MeSH
- aorta patofyziologie MeSH
- bronchiální astma patofyziologie MeSH
- modely nemocí na zvířatech MeSH
- morčata MeSH
- receptor serotoninový 5-HT2A fyziologie MeSH
- serotonin fyziologie MeSH
- svaly hladké cévní patofyziologie MeSH
- zvířata MeSH
- Check Tag
- morčata MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
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 hypertension include increased activity of sympathetic nervous system (SNS), glucocorticoid (GC) overload and altered endothelial function including decreased nitric oxide (NO) bioavailability. Nitric oxide is well known neurotransmitter, neuromodulator and 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.
- MeSH
- buněčný převod mechanických signálů MeSH
- gasotransmitery metabolismus MeSH
- glukokortikoidy metabolismus MeSH
- hypertenze etiologie patofyziologie MeSH
- krevní tlak MeSH
- lidé MeSH
- modely kardiovaskulární MeSH
- oxid dusnatý metabolismus MeSH
- psychický stres komplikace patofyziologie MeSH
- svaly hladké cévní patofyziologie MeSH
- sympatický nervový systém patofyziologie MeSH
- vazodilatace MeSH
- vazomotorický systém patofyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Cardiovascular studies have confirmed that hydrogen sulphide (H(2)S) is involved in various signaling pathways in both physiological and pathological conditions, including hypertension. In contrast to nitric oxide (NO), which has a clear vasorelaxant action, H(2)S has both vasorelaxing and vasoconstricting effects on the cardiovascular system. H(2)S is an important antihypertensive agent, and the reduced production of H(2)S and the alterations in its functions are involved in the initiation of spontaneous hypertension. Moreover, cross-talk between H(2)S and NO has been reported. NO-H(2)S interactions include reactions between the molecules themselves, and each has been shown to regulate the endogenous production of the other. In addition, NO and H(2)S can interact to form a nitrosothiol/s complex, which has original properties and represents a novel nitroso-sulphide signaling pathway. Furthermore, recent results have shown that the interaction between H(2)S and NO could be involved in the endothelium-regulated compensatory mechanisms that are observed in juvenile spontaneously hypertensive rats. The present review is devoted to role of H(2)S in vascular tone regulation. We primarily focus on the mechanisms of H(2)S-NO interactions and on the role of H(2)S in blood pressure regulation in normotensive and spontaneously hypertensive rats.
- MeSH
- buněčný převod mechanických signálů MeSH
- gasotransmitery metabolismus MeSH
- hypertenze patofyziologie MeSH
- krevní tlak * MeSH
- krysa rodu rattus MeSH
- oxid dusnatý metabolismus MeSH
- potkani inbrední SHR MeSH
- sulfan metabolismus MeSH
- svaly hladké cévní patofyziologie MeSH
- vazodilatace MeSH
- vazokonstrikce MeSH
- vazomotorický systém patofyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Pulmonary hypertension (PH), associated with imbalance in vasoactive mediators and massive remodeling of pulmonary vasculature, represents a serious health complication. Despite the progress in treatment, PH patients typically have poor prognoses with severely affected quality of life. Asymmetric dimethyl arginine (ADMA), endogenous inhibitor of endothelial nitric oxide synthase (eNOS), also represents one of the critical regulators of pulmonary vascular functions. The present study describes a novel mechanism of ADMA-induced dysfunction in human pulmonary endothelial and smooth muscle cells. The effect of ADMA was compared with well-established model of hypoxia-induced pulmonary vascular dysfunction. It was discovered for the first time that ADMA induced the activation of signal transducer and activator of transcription 3 (STAT3) and stabilization of hypoxia inducible factor 1α (HIF-1α) in both types of cells, associated with drastic alternations in normal cellular functions (e.g., nitric oxide production, cell proliferation/Ca(2+) concentration, production of pro-inflammatory mediators, and expression of eNOS, DDAH1, and ICAM-1). Additionally, ADMA significantly enhanced the hypoxia-mediated increase in the signaling cascades. In summary, increased ADMA may lead to manifestation of PH phenotype in human endothelial and smooth muscle cells via the STAT3/HIF-1α cascade. Therefore this signaling pathway represents the potential pathway for future clinical interventions in PH.
- MeSH
- amidohydrolasy metabolismus MeSH
- arginin analogy a deriváty farmakologie MeSH
- arteria pulmonalis účinky léků metabolismus patofyziologie MeSH
- endoteliální buňky účinky léků metabolismus MeSH
- faktor 1 indukovatelný hypoxií - podjednotka alfa metabolismus MeSH
- hypoxie buňky MeSH
- kultivované buňky MeSH
- lidé MeSH
- mediátory zánětu metabolismus MeSH
- mezibuněčná adhezivní molekula-1 metabolismus MeSH
- myocyty hladké svaloviny účinky léků metabolismus MeSH
- oxid dusnatý metabolismus MeSH
- plicní hypertenze etiologie metabolismus patofyziologie MeSH
- proliferace buněk účinky léků MeSH
- signální transdukce účinky léků MeSH
- svaly hladké cévní účinky léků metabolismus patofyziologie MeSH
- synthasa oxidu dusnatého, typ III metabolismus MeSH
- transkripční faktor STAT3 metabolismus MeSH
- vápník metabolismus MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- MeSH
- aldosteron fyziologie metabolismus MeSH
- cévní endotel metabolismus patofyziologie MeSH
- hypertenze metabolismus patofyziologie MeSH
- lidé MeSH
- metabolický syndrom metabolismus patofyziologie MeSH
- myokard patologie MeSH
- receptory mineralokortikoidů metabolismus MeSH
- signální transdukce MeSH
- srdce patofyziologie MeSH
- svaly hladké cévní metabolismus patofyziologie MeSH
- zánět patofyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Primární řasinka je mechanosenzorická, solitární, nepohyblivá, mikrotubulární struktura, která se v klidové části buněčného cyklu vyskytuje na povrchu většiny lidských buněk, včetně buněk embryonálních, kmenových, mezenchymálních, fibroblastů, myoblastů, kardiomyocytů, hladkých svalových buněk (leiomyocytů) cévní stěny a buněk endotelu. Primární řasinky se ve zvýšené frekvenci nacházejí i na povrchu buněk endotelu v predilekčních místech aterosklerózy, lipoidních proužků a skvrn a ateromových plátů. Bazálním tělískem primární řasinky je mateřský centriol. V současné době se studuje význam primárních řasinek v mechanobiologii kardiovaskulárního aparátu a jejich vztah k migraci buněk, kontrole buněčného cyklu a aterogenezi. Tématem tohoto přehledového sdělení jsou současné poznatky o primárních řasinkách buněk kardiovaskulárního aparátu. Klíčová slova: primární řasinky – kardiomyocyty – buňky endotelu – hladké svalové buňky (leiomyocyty) cévní stěny – ateroskleróza
The primary cilium is a mechanosensory, solitary, non-motile microtubule-based structure that in the quiescent phase of the cell cycle projects from the surface of the majority of human cells, including embryonal, stem and mesenchymal cells, fibroblasts, myoblasts, cardiomyocytes, vascular smooth muscle and endothelial cells. Primary cilia are in increased frequency also present on the surface of endothelial cells in atherosclerotic predilection sites, lipoid streaks and dots and atheromatous plaques. The primary cilium is formed from the mother centriole. Primary cilia are currently studied in mechanobiology of cardiovascular apparatus and their role in cell migration, cell cycle control and atherogenesis. The aim of this paper is to provide a review of the current knowledge on the primary cilia of cells of cardiovascular apparatus.
- Klíčová slova
- hladké svalové buňky (leiomyocyty) cévní stěny, buňky endotelu,
- MeSH
- aorta MeSH
- ateroskleróza patofyziologie MeSH
- buněčný převod mechanických signálů fyziologie MeSH
- cévní endotel * cytologie fyziologie MeSH
- cilie * fyziologie patologie MeSH
- endoteliální buňky fyziologie patologie MeSH
- epitelo-mezenchymální tranzice fyziologie MeSH
- kardiomyocyty fyziologie MeSH
- lidé MeSH
- mechanický stres MeSH
- myocyty hladké svaloviny patologie MeSH
- pevnost ve smyku MeSH
- svaly hladké cévní * fyziologie patofyziologie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- 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
Practically all mammalian cells including human can switch, according to micro- or macroenvironmental conditions, from states of cellular quiescence to inflammatory activation and vice versa. Along with recent knowledge, cellular quiescence is not a passive, but a highly active state with broad engagement of the cell synthetic and secretory machinery. Inflammatory activation is a beneficial process in cases of infection; however, if its control fails, it may degrade into autoimmune diseases or cancer growth. Control over cellular quiescence is exerted predominantly by a set of zincfinger transcription proteins, referred to as Krüppel-like factors (KLFs). This review article offers recent information concerning activities of Krüppel-like factor 4 in the vascular wall.
- MeSH
- ateroskleróza patofyziologie MeSH
- cévní endotel fyziologie MeSH
- financování organizované MeSH
- lidé MeSH
- svaly hladké cévní fyziologie patofyziologie zranění MeSH
- transkripční faktory Krüppel-like fyziologie MeSH
- zánět patofyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- fibroblastové růstové faktory fyziologie krev MeSH
- finanční podpora výzkumu jako téma MeSH
- fosfor krev metabolismus MeSH
- kalcinóza etiologie prevence a kontrola MeSH
- kalcitriol aplikace a dávkování krev MeSH
- lidé MeSH
- proteiny fyziologie MeSH
- renální insuficience farmakoterapie metabolismus MeSH
- sekundární hyperparatyreóza etiologie MeSH
- svaly hladké cévní patofyziologie MeSH
- vápník krev metabolismus MeSH
- vitamin D analogy a deriváty aplikace a dávkování metabolismus MeSH
- Check Tag
- lidé MeSH
