TY  - JOUR
AU  - Jukic, Ivana
AU  - Mihaljevic, Zrinka
AU  - Matic, Anita
AU  - Mihalj, Martina
AU  - Kozina, Natasa
AU  - Selthofer-Relatic, Kristina
AU  - Mihaljevic, Dubravka
AU  - Koller, Ákos
AU  - Tartaro Bujak, Ivana
AU  - Drenjancevic, Ines
TI  - Angiotensin II type 1 receptor is involved in flow-induced vasomotor responses of isolated middle cerebral arteries. Role of oxidative stress
JF  - AMERICAN JOURNAL OF PHYSIOLOGY: HEART AND CIRCULATORY PHYSIOLOGY
J2  - AM J PHYSIOL HEART C
VL  - 320
PY  - 2021
IS  - 4
SP  - H1609
EP  - H1624
PG  - 16
SN  - 0363-6135
DO  - 10.1152/ajpheart.00620.2020
UR  - https://m2.mtmt.hu/api/publication/31905067
ID  - 31905067
AB  - This study aimed to determine the mechanosensing role of angiotensin II type 1 receptor (AT1R) in flow-induced dilation (FID) and oxidative stress production in middle cerebral arteries (MCA) of Sprague-Dawley rats. Eleven-weeks old, healthy male Sprague-Dawley rats on a standard diet were given the AT1R blocker losartan (1 mg/mL) in drinking water (losartan group) or tap water (control group) ad libitum for 7 days. Blockade of AT1R attenuated FID and acetylcholine-induced dilations was compared to control group. Nitric oxide (NO) synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) and cyclooxygenase inhibitor indomethacin (INDO) significantly reduced FID in control group. The attenuated FID in losartan group was further reduced by INDO only at ∆100 mmHg, whereas L-NAME had no effect. In losartan group, TEMPOL (a superoxide scavenger) restored dilatation, while TEMPOL+L-NAME together significantly reduced FID compared to restored dilatation with TEMPOL alone. Direct fluorescence measurements of NO and reactive oxygen species (ROS) production in MCA, in no-flow conditions revealed significantly reduced vascular NO levels with AT1R blockade compared to control group, while flow increased the NO and ROS production in losartan group and had no effect in control group. In losartan group, TEMPOL decreased ROS production in both no-flow and flow conditions. AT1R blockade elicited increased serum concentrations of AngII, 8-iso-PGF2α, and TBARS, and decreased antioxidant enzyme activity (SOD and CAT). These results suggest that in small isolated cerebral arteries: 1) AT1 receptor maintains dilations in physiological conditions; 2) AT1R blockade leads to increased vascular and systemic oxidative stress, which underlies impaired FID.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Czigler, András
AU  - Tóth, Luca
AU  - Szarka, Nikolett
AU  - Szilágyi, Krisztina
AU  - Kellermayer, Zoltán
AU  - Stayer-Harci, Alexandra
AU  - Vecsernyes, Monika
AU  - Ungvári, Zoltán István
AU  - Szolics, Alex
AU  - Koller, Ákos
AU  - Büki, András
AU  - Tóth, Péter József
TI  - Prostaglandin E2, a postulated mediator of neurovascular coupling, at low concentrations dilates whereas at higher concentrations constricts human cerebral parenchymal arterioles
JF  - PROSTAGLANDINS & OTHER LIPID MEDIATORS
J2  - PROSTAG OTH LIPID M
VL  - 146
PY  - 2020
PG  - 7
SN  - 1098-8823
DO  - 10.1016/j.prostaglandins.2019.106389
UR  - https://m2.mtmt.hu/api/publication/30886434
ID  - 30886434
AB  - There is considerable controversy regarding the vasoactive action of prostaglandin E2 (PGE2). On the one hand, indirect evidence implicates that astrocytic release of PGE2 contributes to neurovascular coupling responses mediating functional hyperemia in the brain. On the other hand, overproduction of PGE2 was also reported to contribute to cerebral vasospasm associated with subarachnoid hemorrhage. The present study was conducted to resolve this controversy by determining the direct vasoactive effects of PGE2 in resistance-sized human cerebral parenchymal arterioles. To achieve this goal PGE2-induced isotonic vasomotor responses were assessed in parenchymal arterioles isolated from fronto-temporo-parietal cortical tissues surgically removed from patients and expression of PGE2 receptors were examined. In functionally intact parenchymal arterioles lower concentrations of PGE2 (from 10-8 to 10-6 mol/l) caused significant, endothelium-independent vasorelaxation, which was inhibited by the EP4 receptor blocker BGC201531. In contrast, higher concentrations of PGE2 evoked significant EP1-dependent vasoconstriction, which could not be reversed by the EP4 receptor agonist CAY10598. We also confirmed previous observations that PGE2 primarily evokes constriction in intracerebral arterioles isolated from R. norvegicus. Importantly, vascular mRNA and protein expression of vasodilator EP4 receptors was significantly higher than that of vasoconstrictor EP1 receptors in human cerebral arterioles. PGE2 at low concentrations dilates whereas at higher concentrations constricts human cerebral parenchymal arterioles. This bimodal vasomotor response is consistent with both the proposed vasodilator role of PGE2 during functional hyperemia and its putative role in cerebral vasospasm associated with subarachnoid hemorrhage in human patients.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Czigler, András
AU  - Tóth, Luca
AU  - Szarka, Nikolett
AU  - Berta, Gergely
AU  - Amrein, Krisztina
AU  - Czeiter, Endre
AU  - Lendvai-Emmert, Dominika
AU  - Bodó, Kornélia
AU  - Tarantini, Stefano
AU  - Koller, Ákos
AU  - Ungvári, Zoltán István
AU  - Büki, András
AU  - Tóth, Péter József
TI  - Hypertension exacerbates cerebrovascular oxidative stress induced by mild traumatic brain injury : protective effects of the mitochondria-targeted antioxidative peptide SS-31
JF  - JOURNAL OF NEUROTRAUMA
J2  - J NEUROTRAUM
VL  - 36
PY  - 2019
IS  - 23
SP  - 3309
EP  - 3315
PG  - 7
SN  - 0897-7151
DO  - 10.1089/neu.2019.6439
UR  - https://m2.mtmt.hu/api/publication/30734491
ID  - 30734491
AB  - Traumatic brain injury (TBI) induces cerebrovascular oxidative stress, which is associated with neurovascular uncoupling, autoregulatory dysfunction and persisting cognitive decline in both preclinical models and patients. However, single mild TBI, the most frequent form of brain trauma increases cerebral generation of reactive oxygen species (ROS) only transiently. We hypothesized, that co-morbid conditions may exacerbate long term ROS generation in cerebral arteries after mTBI. Since hypertension is the most important cerebrovascular risk factor in populations prone to mild brain trauma, we induced mTBI in normotensive and spontaneously hypertensive rats (SHR) and assessed changes in cytoplasmic and mitochondrial superoxide (O2-) production by confocal microscopy in isolated middle cerebral arteries (MCA) two weeks after mTBI using dihydroethidine (DHE) and the mitochondria-targeted redox sensitive fluorescent indicator dye MitoSox. We found that mTBI induced a significant increase in long term cytoplasmic and mitochondrial O2- production in MCAs of SHRs and increased expression of the NADPH oxidase subunit Nox4, which were reversed to the normal level by treating the animals with the cell-permeable, mitochondria-targeted antioxidant peptide SS-31(5.7 mg kg-1 day-1 , i.p.). Persistent mTBI-induced oxidative stress in MCAs of SHRs was significantly decreased by inhibiting vascular NADPH oxidase (apocyinin). We propose, that hypertension- and mTBI-induced cerebrovascular oxidative stress likely lead to persistent dysregulation of CBF and cognitive dysfunction, which might be reversed by SS-31 treatment.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Szarka, Nikolett
AU  - Tóth, Luca
AU  - Czigler, András
AU  - Kellermayer, Zoltán
AU  - Ungvári, Zoltán István
AU  - Amrein, Krisztina
AU  - Czeiter, Endre
AU  - Bali, Zsolt Kristóf
AU  - Tadepalli, Sai Ambika
AU  - Wahr, Mátyás
AU  - Hernádi, István
AU  - Koller, Ákos
AU  - Büki, András
AU  - Tóth, Péter József
TI  - Single Mild Traumatic Brain Injury Induces Persistent Disruption of the Blood-Brain Barrier, Neuroinflammation and Cognitive Decline in Hypertensive Rats
JF  - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
J2  - INT J MOL SCI
VL  - 20
PY  - 2019
IS  - 13
PG  - 10
SN  - 1661-6596
DO  - 10.3390/ijms20133223
UR  - https://m2.mtmt.hu/api/publication/30727304
ID  - 30727304
N1  - * Megosztott szerzőség
AB  - Traumatic brain injury (TBI) induces blood-brain barrier (BBB) disruption, which contributes to secondary injury of brain tissue and development of chronic cognitive decline. However, single mild (m)TBI, the most frequent form of brain trauma disrupts the BBB only transiently. We hypothesized, that co-morbid conditions exacerbate persistent BBB disruption after mTBI leading to long term cognitive dysfunction. Since hypertension is the most important cerebrovascular risk factor in populations prone to mild brain trauma, we induced mTBI in normotensive Wistar and spontaneously hypertensive rats (SHR) and we assessed BBB permeability, extravasation of blood-borne substances, neuroinflammation and cognitive function two weeks after trauma. We found that mTBI induced a significant BBB disruption two weeks after trauma in SHRs but not in normotensive Wistar rats, which was associated with a significant accumulation of fibrin and increased neuronal expression of inflammatory cytokines TNFα, IL-1β and IL-6 in the cortex and hippocampus. SHRs showed impaired learning and memory two weeks after mild TBI, whereas cognitive function of normotensive Wistar rats remained intact. Future studies should establish the mechanisms through which hypertension and mild TBI interact to promote persistent BBB disruption, neuroinflammation and cognitive decline to provide neuroprotection and improve cognitive function in patients with mTBI.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Szarka, Nikolett
AU  - Amrein, Krisztina
AU  - Horváth, Péter
AU  - Ivic, Ivan
AU  - Czeiter, Endre
AU  - Büki, András
AU  - Koller, Ákos
AU  - Tóth, Péter József
TI  - HYPERTENSION-INDUCED ENHANCED MYOGENIC CONSTRICTION OF CEREBRAL ARTERIES IS PRESERVED AFTER TRAUMATIC BRAIN INJURY.
JF  - JOURNAL OF NEUROTRAUMA
J2  - J NEUROTRAUM
VL  - 34
PY  - 2017
IS  - 14
SP  - 2315
EP  - 2319
PG  - 5
SN  - 0897-7151
DO  - 10.1089/neu.2016.4962
UR  - https://m2.mtmt.hu/api/publication/3195505
ID  - 3195505
AB  - Traumatic brain injury (TBI) was shown to impair pressure-induced myogenic response of cerebral arteries, which is associated with vascular and neural dysfunction and increased mortality of TBI patients. Hypertension was shown to enhance myogenic tone of cerebral arteries via increased vascular production of 20-hydroxyeicosatrienoic acid (HETE). This adaptive mechanism protects brain tissue form pressure/volume overload, but it can also lead to increased susceptibility to cerebral ischemia. Although both effects may potentiate the detrimental vascular consequences of TBI, it is not known how hypertension modulates the effect of TBI on myogenic responses of cerebral vessels. We hypothesized that in hypertensive rats, the enhanced myogenic cerebrovascular response is preserved after TBI. Thus, we investigated the myogenic responses of isolated middle cerebral arteries (MCA) of normotensive and spontaneously hypertensive rats (SHR) after severe impact acceleration diffuse brain injury. TBI diminished myogenic constriction of MCAs isolated from normotensive rats, whereas the 20-HETE-mediated enhanced myogenic response of MCAs isolated from SHRs was not affected by TBI. These results suggest that the optimal cerebral perfusion pressure values and vascular signaling pathways can be different and thus should be targeted differently in normotensive and hypertensive patients following TBI.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Cséplő, Péter
AU  - Vámos, Zoltán
AU  - Török, Orsolya
AU  - Ivic, Ivan
AU  - Tóth, Attila
AU  - Büki, András
AU  - Koller, Ákos
TI  - Hemolyzed Blood Elicits a Calcium Antagonist and High CO2 Reversible Constriction via Elevation of [Ca2+]i in Isolated Cerebral Arteries : Perivascular Blood Constricts Cerebral Arteries
JF  - JOURNAL OF NEUROTRAUMA
J2  - J NEUROTRAUM
VL  - 34
ET  - 0
PY  - 2017
IS  - 2
SP  - 529
EP  - 534
PG  - 6
SN  - 0897-7151
DO  - 10.1089/neu.2015.4365
UR  - https://m2.mtmt.hu/api/publication/3065264
ID  - 3065264
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Cséplő, Péter
AU  - Vámos, Zoltán
AU  - Ivic, Ivan
AU  - Török, Orsolya
AU  - Tóth, Attila
AU  - Koller, Ákos
TI  - The Beta-1-Receptor Blocker Nebivolol Elicits Dilation of Cerebral Arteries by Reducing Smooth Muscle [Ca2+]i
JF  - PLOS ONE
J2  - PLOS ONE
VL  - 11
PY  - 2016
IS  - 10
PG  - 22
SN  - 1932-6203
DO  - 10.1371/journal.pone.0164010
UR  - https://m2.mtmt.hu/api/publication/3122786
ID  - 3122786
AB  - Rationale Nebivolol is known to have beta-1 blocker activity, but it was also suggested that it elicits relaxation of the peripheral arteries in part via release of nitric oxide (NO). However, the effect of nebivolol on the vasomotor tone of cerebral arteries is still unclear. Objective To assess the effects of nebivolol on the diameter of isolated rat basilar arteries (BA) in control, in the presence of inhibitors of vasomotor signaling pathways of know action and hemolysed blood. Methods and Results Vasomotor responses were measured by videomicroscopy and the intracellular Ca 2+ by the Fura-2 AM ratiometric method. Under control conditions, nebivolol elicited a substantial dilation of the BA (from 216+/-22 to 394+/-20 mu m; p< 0.05) in a concentration-dependent manner (10(-7) to 10(-4) M). The dilatation was significantly reduced by endothelium denudation or by L-NAME (inhibitor of NO synthase) or by SQ22536 (adenylyl cyclase blocker). Dilatation of BA was also affected by beta-2 receptor blockade with butoxamine, but not by the guanylate cyclase blocker ODQ. Interestingly, beta-1 blockade by atenolol inhibited nebivololinduced dilation. Also, the BKCa channel blocker iberiotoxin and KCa channel inhibitor TEA significantly reduced nebivolol-induced dilation. Nebivolol significantly reduced smooth muscle Ca 2+ level, which correlated with the increases in diameters and moreover it reversed the hemolysed blood-induced constriction of BA. Conclusions Nebivolol seems to have an important dilator effect in cerebral arteries, which is mediated via several vasomotor mechanisms, converging on the reduction of smooth muscle Ca2+ levels. As such, nebivolol may be effective to improve cerebral circulation in various diseased conditions, such as hemorrhage.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Németh, Zoltán
AU  - Cziráki, Attila
AU  - Szabados, Sándor
AU  - Biri, B
AU  - Kéki, Sándor
AU  - Koller, Ákos
TI  - Elevated Levels of Asymmetric Dimethylarginine (ADMA) in the Pericardial Fluid of Cardiac Patients Correlate with Cardiac Hypertrophy.
JF  - PLOS ONE
J2  - PLOS ONE
VL  - 10
PY  - 2015
IS  - 8
PG  - 19
SN  - 1932-6203
DO  - 10.1371/journal.pone.0135498
UR  - https://m2.mtmt.hu/api/publication/2938981
ID  - 2938981
AB  - BACKGROUND: Pericardial fluid (PF) contains several biologically active substances, which may provide information regarding the cardiac conditions. Nitric oxide (NO) has been implicated in cardiac remodeling. We hypothesized that L-arginine (L-Arg) precursor of NO-synthase (NOS) and asymmetric dimethylarginine (ADMA), an inhibitor of NOS, are present in PF of cardiac patients and their altered levels may contribute to altered cardiac morphology. METHODS: L-Arg and ADMA concentrations in plasma and PF, and echocardiographic parameters of patients undergoing coronary artery bypass graft (CABG, n = 28) or valve replacement (VR, n = 25) were determined. RESULTS: We have found LV hypertrophy in 35.7% of CABG, and 80% of VR patients. In all groups, plasma and PF L-Arg levels were higher than that of ADMA. Plasma L-Arg level was higher in CABG than VR (75.7+/-4.6 mumol/L vs. 58.1+/-4.9 mumol/L, p = 0.011), whereas PF ADMA level was higher in VR than CABG (0.9+/-0.0 mumol/L vs. 0.7+/-0.0 mumol/L, p = 0.009). L-Arg/ADMA ratio was lower in the VR than CABG (VRplasma: 76.1+/-6.6 vs. CABGplasma: 125.4+/-10.7, p = 0.004; VRPF: 81.7+/-4.8 vs. CABGPF: 110.4+/-7.2, p = 0.009). There was a positive correlation between plasma L-Arg and ADMA in CABG (r = 0.539, p = 0.015); and plasma and PF L-Arg in CABG (r = 0.357, p = 0.031); and plasma and PF ADMA in VR (r = 0.529, p = 0.003); and PF L-Arg and ADMA in both CABG and VR (CABG: r = 0.468, p = 0.006; VR: r = 0.371, p = 0.034). The following echocardiographic parameters were higher in VR compared to CABG: interventricular septum (14.7+/-0.5 mm vs. 11.9+/-0.4 mm, p = 0.000); posterior wall thickness (12.6+/-0.3 mm vs. 11.5+/-0.2 mm, p = 0.000); left ventricular (LV) mass (318.6+/-23.5 g vs. 234.6+/-12.3 g, p = 0.007); right ventricular (RV) (33.9+/-0.9 cm2 vs. 29.7+/-0.7 cm2, p = 0.004); right atrial (18.6+/-1.0 cm2 vs. 15.4+/-0.6 cm2, p = 0.020); left atrial (19.8+/-1.0 cm2 vs. 16.9+/-0.6 cm2, p = 0.033) areas. There was a positive correlation between plasma ADMA and RV area (r = 0.453, p = 0.011); PF ADMA and end-diastolic (r = 0.434, p = 0.015) and systolic diameter of LV (r = 0.487, p = 0.007); and negative correlation between PF ADMA and LV ejection fraction (r = -0.445, p = 0.013) in VR. CONCLUSION: We suggest that elevated levels of ADMA in the PF of patients indicate upregulated RAS and reduced bioavailability of NO, which can contribute to the development of cardiac hypertrophy and remodeling.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Tóth, Péter József
AU  - Tarantini, Stefano
AU  - Ashpole, NM
AU  - Tucsek, Z
AU  - Milne, GL
AU  - Valcarcel-Ares, NM
AU  - Menyhárt, Ákos
AU  - Farkas, Eszter
AU  - Sonntag, WE
AU  - Csiszar, Anna
AU  - Ungvári, Zoltán István
TI  - IGF-1 deficiency impairs neurovascular coupling in mice: implications for cerebromicrovascular aging
JF  - AGING CELL
J2  - AGING CELL
VL  - 14
PY  - 2015
IS  - 6
SP  - 1034
EP  - 1044
PG  - 11
SN  - 1474-9718
DO  - 10.1111/acel.12372
UR  - https://m2.mtmt.hu/api/publication/2920558
ID  - 2920558
N1  - * Megosztott szerzőség
AB  - Aging is associated with marked deficiency in circulating IGF-1, which has been shown to contribute to age-related cognitive decline. Impairment of moment-to-moment adjustment of cerebral blood flow (CBF) via neurovascular coupling is thought to play a critical role in the genesis of age-related cognitive impairment. To establish the link between IGF-1 deficiency and cerebromicrovascular impairment, neurovascular coupling mechanisms were studied in a novel mouse model of IGF-1 deficiency (Igf1f/f -TBG-Cre-AAV8) and accelerated vascular aging. We found that IGF-1-deficient mice exhibit neurovascular uncoupling and show a deficit in hippocampal-dependent spatial memory test, mimicking the aging phenotype. IGF-1 deficiency significantly impaired cerebromicrovascular endothelial function decreasing NO mediation of neurovascular coupling. IGF-1 deficiency also impaired glutamate-mediated CBF responses, likely due to dysregulation of astrocytic expression of metabotropic glutamate receptors and impairing mediation of CBF responses by eicosanoid gliotransmitters. Collectively, we demonstrate that IGF-1 deficiency promotes cerebromicrovascular dysfunction and neurovascular uncoupling mimicking the aging phenotype, which are likely to contribute to cognitive impairment.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Németh, Zoltán
AU  - Cziráki, Attila
AU  - Szabados, Sándor
AU  - Horváth, Iván
AU  - Koller, Ákos
TI  - Pericardial fluid of cardiac patients elicits arterial constriction: role of endothelin-1
JF  - CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
J2  - CAN J PHYSIOL PHARM
VL  - 93
PY  - 2015
IS  - 9
SP  - 779
EP  - 785
PG  - 7
SN  - 0008-4212
DO  - 10.1139/cjpp-2015-0030
UR  - https://m2.mtmt.hu/api/publication/2907167
ID  - 2907167
LA  - English
DB  - MTMT
ER  -