Atrial fibrillation is associated with atrial remodeling, in which connexin 43 (Cx43) and cell hypertrophy play important roles. In this study, apelin-13, an aliphatic peptide, was used to explore the protective effects of the adenosine monophosphate-activated protein kinase (AMPK)/mTOR signaling pathway on Cx43 expression and autophagy, using murine atrial HL-1 cells. The expression of Cx43, AMPK, B-type natriuretic peptide (BNP) and pathway-related proteins was detected by Western blot analysis. Cellular fluorescence imaging was used to visualize Cx43 distribution and the cytoskeleton. Our results showed that the Cx43 expression was significantly decreased in HL-1 cells treated with angiotensin II but increased in cells additionally treated with apelin-13. Meanwhile, apelin-13 decreased BNP expression and increased AMPK expression. However, the expression of Cx43 and LC3 increased by apelin-13 was inhibited by treatment with compound C, an AMPK inhibitor. In addition, rapamycin, an mTOR inhibitor, promoted the development of autophagy, further inhibited the protective effect on Cx43 expression and increased cell hypertrophy. Thus, apelin-13 enhances Cx43 expression and autophagy via the AMPK/mTOR signaling pathway, and serving as a potential therapeutic target for atrial fibrillation.

• MeSH
• angiotensin II farmakologie   MeSH
• autofagie účinky léků   MeSH
• buněčné linie MeSH
• down regulace účinky léků   MeSH
• fibrilace síní metabolismus   patologie   prevence a kontrola   MeSH
• kardiomyocyty účinky léků   metabolismus   patologie   MeSH
• konexin 43 metabolismus   MeSH
• lékové interakce MeSH
• mezibuněčné signální peptidy a proteiny farmakologie   MeSH
• myši MeSH
• proteinkinasy aktivované AMP metabolismus   MeSH
• signální transdukce účinky léků   MeSH
• TOR serin-threoninkinasy metabolismus   MeSH
• vazokonstriktory farmakologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• Klíčová slova
• retrakce,
• MeSH
• adrenalin farmakologie   klasifikace   škodlivé účinky   terapeutické užití   MeSH
• adrenergní látky farmakologie   klasifikace   škodlivé účinky   terapeutické užití   MeSH
• adstringencia farmakologie   klasifikace   terapeutické užití   MeSH
• agonisté adrenergních receptorů farmakologie   klasifikace   škodlivé účinky   terapeutické užití   MeSH
• gingiva MeSH
• hemostatické techniky klasifikace   škodlivé účinky   MeSH
• hemostatika * farmakologie   klasifikace   škodlivé účinky   terapeutické užití   MeSH
• lidé MeSH
• stomatologická protetika metody   MeSH
• terapie měkkých tkání metody   ošetřování   MeSH
• vazokonstriktory farmakologie   klasifikace   škodlivé účinky   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

The effect of chemical sympathectomy on cardiovascular parameters and the compensatory role of adrenal hormones, the renin-angiotensin system, and cardiovascular sensitivity to vasoconstrictors were studied in spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats. Sympathectomy was induced in 20-week-old rats by daily intraperitoneal guanethidine administration (30 mg/kg b.w.) for 2 weeks. Basal blood pressure (BP), heart rate (HR), and restraint stress-induced cardiovascular changes were measured by radiotelemetry. The BP response to catecholamines was determined in rats with implanted catheters. Sympathectomy decreased BP only transiently, and after 14-day guanethidine treatment, BP returned to basal values in both strains. Sympathectomy permanently lowered HR, improved baroreflex sensitivity, and decreased the low-frequency domain of systolic blood pressure variability (a marker of vascular sympathetic activity). Guanethidine also attenuated the BP and HR responses to restraint stress. On the other hand, the BP response to catecholamines was augmented in sympathectomized rats, and this was not due to the de novo synthesis of vascular adrenergic receptors. Sympathectomy caused adrenal enlargement, enhanced the expression of adrenal catecholamine biosynthetic enzymes, and elevated plasma adrenaline levels in both strains, especially in WKY rats. Guanethidine also increased the plasma levels of aldosterone and corticosterone in WKY rats only. In conclusion, sympathectomy produced a transient decrease in BP, a chronic decrease in HR and improvement in baroreflex sensitivity. The effect of sympathectomy on BP was counteracted by increased vascular sensitivity to catecholamines in WKY rats and SHRs and/or by the enhanced secretion of adrenal hormones, which was more pronounced in WKY rats.

• MeSH
• baroreflex účinky léků   MeSH
• cévy účinky léků   inervace   patofyziologie   MeSH
• fyzické omezení MeSH
• guanethidin farmakologie   MeSH
• hypertenze patofyziologie   MeSH
• kardiovaskulární fyziologické jevy účinky léků   MeSH
• katecholaminy metabolismus   MeSH
• krevní tlak účinky léků   MeSH
• krysa rodu rattus MeSH
• nadledviny růst a vývoj   metabolismus   patofyziologie   MeSH
• potkani inbrední SHR MeSH
• potkani inbrední WKY MeSH
• psychický stres MeSH
• srdeční frekvence účinky léků   MeSH
• sympatolytika farmakologie   MeSH
• vazokonstriktory farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVE: We evaluated the hypothesis that the development of renal dysfunction and congestive heart failure (CHF) caused by volume overload in rats with angiotensin II (ANG II)-dependent hypertension is associated with altered renal vascular responsiveness to ANG II and to epoxyeicosatrienoic acids (EETs). METHODS: Ren-2 transgenic rats (TGRs) were used as a model of ANG II-dependent hypertension. CHF was induced by volume overload achieved by the creation of the aorto-caval fistula (ACF). Renal blood flow (RBF) responses were determined to renal arterial administration of ANG II, native 11,12-EET, an analog of 14,15-EETs (EET-A), norepinephrine (NE), acetylcholine (Ach) and bradykinin (Bk) in healthy (i.e., sham-operated) TGR and ACF TGR (5 weeks after ACF creation). RESULTS: Selective intrarenal administration of neither vasoactive drug altered mean arterial pressure in any group. Administration of ANG II caused greater decreases in RBF in ACF TGR than in sham-operated TGR, whereas after administration of NE the respective decreases were comparable in the 2 groups. Administration of Ach and Bk elicited significantly higher RBF increases in ACF TGR as compared with sham-operated TGR. In contrast, administration of 11,12-EET and EET-A caused significantly smaller RBF increases in ACF TGR than in sham-operated TGR. CONCLUSION: The findings show that 5 weeks after creation of ACF, the TGR exhibit exaggerated renal vasoconstrictor responses to ANG II and reduced renal vasodilatory responses to EETs, suggesting that both these alterations might play an important role in the development of renal dysfunction in this model of CHF.

• MeSH
• angiotensin II škodlivé účinky   MeSH
• arteria pulmonalis abnormality   patofyziologie   MeSH
• arterioarteriální píštěl patofyziologie   MeSH
• hypertenze chemicky indukované   komplikace   MeSH
• krysa rodu rattus MeSH
• potkani transgenní MeSH
• renální oběh účinky léků   MeSH
• srdeční selhání komplikace   patofyziologie   MeSH
• vazodilatace účinky léků   MeSH
• vazokonstrikce účinky léků   MeSH
• vazokonstriktory farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• bolest etiologie   MeSH
• diagnostické techniky kardiovaskulární klasifikace   MeSH
• diagnostické zobrazování klasifikace   MeSH
• diferenciální diagnóza MeSH
• lidé MeSH
• onemocnění periferních arterií * diagnóza   farmakoterapie   klasifikace   terapie   MeSH
• oscilometrie MeSH
• stupeň závažnosti nemoci MeSH
• vazokonstriktory aplikace a dávkování   farmakologie   klasifikace   MeSH
• Check Tag
• lidé MeSH

BACKGROUND: Before arterial cannulation for invasive blood pressure monitoring, clinical decision-making depends on non-invasive blood pressure in critically ill patients. Whether non-invasive blood pressure is comparable to invasive measurement is not clearly elucidated. We address this issue as it relates to the use of norepinephrine in patients with cardiogenic shock. METHODS: We analysed invasive and non-invasive blood pressure in 85 patients admitted to the Coronary-Care Unit for cardiogenic shock. We compared initial blood pressure measurement (just after radial artery cannulation) and blood pressure taken during the first 72 hours after admission. Invasive blood pressure was used as the reference method. RESULTS: Initial invasive mean and systolic arterial pressures were in a good agreement with oscillometric blood pressure; mean differences were -0.4 ± 8.8 and +6.1 ± 14.4 mmHg with correlation coefficients of 0.76 and 0.74. Doses of norepinephrine were significant negative determinants of invasive/oscillometric blood pressure differences. The invasive/oscillometric mean arterial pressures and SBP differences were +0.1 ± 3.4 and 7.6 ± 1.6 mmHg in patients treated with nothing or a maximum norepinephrine dose of 0.6 µg/kg/min. However, treatment with very high doses of norepinephrine was associated with a steep rise in mean arterial pressures and SBP invasive/oscillometric differences (-9.5 ± 3.3 and -8.5 ± 5.2 mmHg). In a total of 967 sets of blood pressure measurements, invasive/oscillometric differences were relatively stable across blood pressure categories, with the exception of measurements assessed after very high norepinephrine doses. CONCLUSIONS: Non-invasive BP is a sufficient substitute for invasive measurement in cardiogenic shock patients, with the exception of those receiving very high doses of norepinephrine.

• MeSH
• arteriální tlak MeSH
• kardiogenní šok patofyziologie   MeSH
• katetrizace MeSH
• krevní tlak účinky léků   MeSH
• kritický stav MeSH
• lidé středního věku MeSH
• lidé MeSH
• měření krevního tlaku metody   MeSH
• monitorování fyziologických funkcí MeSH
• noradrenalin aplikace a dávkování   farmakologie   MeSH
• oscilometrie metody   MeSH
• prospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vazokonstriktory aplikace a dávkování   farmakologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

BACKGROUND: Vasopressors and inotropes remain a cornerstone in stabilization of the severely impaired hemodynamics and cardiac output in cardiogenic shock (CS). The aim of this study was to analyze current real-life use of these medications, and their impact on outcome and on changes in cardiac and renal biomarkers over time in CS. METHODS: The multinational CardShock study prospectively enrolled 219 patients with CS. The use of vasopressors and inotropes was analyzed in relation to the primary outcome, i.e., 90-day mortality, with propensity score methods in 216 patients with follow-up data available. Changes in cardiac and renal biomarkers over time until 96 hours from baseline were analyzed with linear mixed modeling. RESULTS: Patients were 67 (SD 12) years old, 26 % were women, and 28 % had been resuscitated from cardiac arrest prior to inclusion. On average, systolic blood pressure was 78 (14) and mean arterial pressure 57 (11) mmHg at detection of shock. 90-day mortality was 41 %. Vasopressors and/or inotropes were administered to 94 % of patients and initiated principally within the first 24 hours. Noradrenaline and adrenaline were given to 75 % and 21 % of patients, and 30 % received several vasopressors. In multivariable logistic regression, only adrenaline (21 %) was independently associated with increased 90-day mortality (OR 5.2, 95 % CI 1.88, 14.7, p = 0.002). The result was independent of prior cardiac arrest (39 % of patients treated with adrenaline), and the association remained in propensity-score-adjusted analysis among vasopressor-treated patients (OR 3.0, 95 % CI 1.3, 7.2, p = 0.013); this was further confirmed by propensity-score-matched analysis. Adrenaline was also associated, independent of prior cardiac arrest, with marked worsening of cardiac and renal biomarkers during the first days. Dobutamine and levosimendan were the most commonly used inotropes (49 % and 24 %). There were no differences in mortality, whether noradrenaline was combined with dobutamine or levosimendan. CONCLUSION: Among vasopressors and inotropes, adrenaline was independently associated with 90-day mortality in CS. Moreover, adrenaline use was associated with marked worsening in cardiac and renal biomarkers. The combined use of noradrenaline with either dobutamine or levosimendan appeared prognostically similar.

• MeSH
• adrenalin škodlivé účinky   farmakologie   terapeutické užití   MeSH
• dospělí MeSH
• hemodynamika fyziologie   MeSH
• kardiogenní šok komplikace   farmakoterapie   MeSH
• kardiotonika farmakokinetika   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mortalita v nemocnicích MeSH
• přežití tkáně účinky léků   MeSH
• senioři MeSH
• tendenční skóre MeSH
• vazokonstriktory škodlivé účinky   farmakologie   terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

This study investigates the effects of long-term treatment with sulodexide (SLX) on norepinephrine (NE)-induced contractions, acetylcholine(Ach)-induced relaxations, acute cyclooxygenase blockade by diclofenac (DIC) in isolated femoral arteries (FA) and the parameters of oxidative phosporylation in liver mitochondria. 15-weeks old Wistar rats were divided into four groups: control (C; injected with saline solution), treated control (C+SLX), diabetic (DM) and treated diabetic (DM+SLX). Diabetes was induced with a single i.v. dose of streptozotocin (STZ) 45 mg.kg(-1). SLX was administered i.p., at dose 100 IU.kg(-1) daily for 5 weeks. Vascular responses of isolated femoral arteries were measured using Mulvany-Halpern myograph. Respiratory function of the mitochondria was determined using voltamperometric method on oxygraph Gilson. In diabetic rats the amplitude of maximal response to NE was elevated. DIC pretreatment decreased the amplitudes of NE-induced contractions in all groups of rats. SLX treatment decreased sensitivity of FA to NE and caused higher relaxatory responses to Ach in C and DM. Oxygen consumption and phosphorylation rates ([QO(2)(S(3))], [QO(2)(S(4))] and (OPR)) and respiratory control ratio (RCR) were decreased in the mitochondria of DM rats. Mitochondria of C rats were not affected with SLX treatment. Administration of SLX in DM rats was associated with increase of RCR, other parameters were not affected. Our findings suggest that SLX treatment might be associated with vasculoprotective effects during diabetes and improvement of mitochondrial function.

• MeSH
• cévní endotel účinky léků   fyziologie   MeSH
• experimentální diabetes mellitus farmakoterapie   metabolismus   patologie   MeSH
• glykosaminoglykany farmakologie   terapeutické užití   MeSH
• jaterní mitochondrie účinky léků   metabolismus   MeSH
• krysa rodu rattus MeSH
• orgánové kultury - kultivační techniky MeSH
• potkani Wistar MeSH
• vazodilatancia farmakologie   terapeutické užití   MeSH
• vazokonstriktory farmakologie   terapeutické užití   MeSH
• výsledek terapie MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

STR/N is an inbred strain of mice which is known to exhibit extreme polydipsia and polyuria. We previously found central administration of angiotensin II enhanced cardiovascular responses in STR/N mice than normal mice, suggesting that STR/N mice might exhibit different cardiovascular responses. Therefore, in this study, we investigated daily mean arterial blood pressure and heart rate, and changes in the baroreceptor-heart rate reflex in conscious STR/N mice and control (ICR) mice. We found that variability in daily mean arterial blood pressure and heart rate was significantly larger in STR/N mice than in ICR mice (p<0.05). There was a stronger response to phenylephrine (PE) in STR/N mice than in ICR mice. For baroreceptor reflex sensitivity, in the rapid response period, the slopes of PE and sodium nitroprusside (SNP) were more negative in STR/N mice than in ICR mice. In the later period, the slopes of PE and SNP were negatively correlated between heart rate and blood pressure in ICR mice, but their slopes were positively correlated in STR/N mice. These results indicated that STR/N mice exhibited the different cardiovascular responses than ICR mice, suggesting that the dysfunction of baroreceptor reflex happened in conscious STR/N mice.

• MeSH
• baroreflex účinky léků   MeSH
• fenylefrin farmakologie   MeSH
• krevní tlak MeSH
• myši inbrední ICR MeSH
• myši MeSH
• nitroprusid farmakologie   MeSH
• polydipsie genetika   patofyziologie   MeSH
• presoreceptory patofyziologie   MeSH
• srdeční frekvence * účinky léků   MeSH
• vazodilatancia farmakologie   MeSH
• vazokonstriktory farmakologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Oxidative stress is an imbalance between free radicals and antioxidants, and is an important etiological factor in the development of hypertension. Recent experimental evidence suggests that subpressor doses of angiotensin II elevate oxidative stress and blood pressure. We aimed to investigate the oxidative stress related mechanism by which a subpressor dose of angiotensin II induces hypertension in a normotensive rat model. Normotensive male Wistar rats were infused with a subpressor dose of angiotensin II for 28 days. The control group was sham operated and infused with saline only. Plasma angiotensin II and H2O2 levels, whole-blood glutathione peroxidase, and AT-1a, Cu/Zn SOD, and p22phox mRNA expression in the aorta was assessed. Systolic and diastolic blood pressures were elevated in the experimental group. There was no change in angiotensin II levels, but a significant increase in AT-1a mRNA expression was found in the experimental group. mRNA expression of p22phox was increased significantly and Cu/Zn SOD decreased significantly in the experimental group. There was no significant change to the H2O2 and GPx levels. Angiotensin II manipulates the free radical-antioxidant balance in the vasculature by selectively increasing O2(-) production and decreasing SOD activity and causes an oxidative stress induced elevation in blood pressure in the Wistar rat.

• MeSH
• angiotensin II krev   farmakologie   MeSH
• glutathionperoxidasa krev   MeSH
• hypertenze chemicky indukované   patofyziologie   MeSH
• krevní tlak účinky léků   MeSH
• krysa rodu rattus MeSH
• messenger RNA biosyntéza   genetika   MeSH
• oxidační stres účinky léků   MeSH
• peroxid vodíku krev   MeSH
• potkani Wistar MeSH
• superoxiddismutasa metabolismus   MeSH
• vazokonstriktory farmakologie   MeSH
• volné radikály metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH