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 - Ivic, Ivan AU - Balaskó, Márta AU - Fülöp, Balázs Dániel AU - Hashimoto, Hitoshi AU - Tóth, Gábor AU - Tamás, Andrea AU - Juhász, Tamás AU - Koller, Ákos AU - Reglődi, Dóra AU - Varjú-Solymár, Margit TI - VPAC1 receptors play a dominant role in PACAP-induced vasorelaxation in female mice JF - PLOS ONE J2 - PLOS ONE VL - 14 ET - 0 PY - 2019 IS - 1 PG - 21 SN - 1932-6203 DO - 10.1371/journal.pone.0211433 UR - https://m2.mtmt.hu/api/publication/30413407 ID - 30413407 N1 - * Megosztott szerzőség AB - PACAP and VIP are closely related neuropeptides with wide distribution and potent effect in the vasculature. We previously reported vasomotor activity in peripheral vasculature of male wild type (WT) and PACAP-deficient (KO) mice. However, female vascular responses are still unexplored. We hypothesized that PACAP-like activity is maintained in female PACAP KO mice and the mechanism through which it is regulated differs from that of male PACAP KO animals.We investigated the vasomotor effects of VIP and PACAP isoforms and their selective blockers in WT and PACAP KO female mice in carotid and femoral arteries. The expression and level of different PACAP receptors in the vessels were measured by RT-PCR and Western blot.In both carotid and femoral arteries of WT mice, PACAP1-38, PACAP1-27 or VIP induced relaxation, without pronounced differences between them. Reduced relaxation was recorded only in the carotid arteries of KO mice as compared to their WT controls. The specific VPAC1R antagonist completely blocked the PACAP/VIP-induced relaxation in both arteries of all mice, while PAC1R antagonist affected relaxation only in their femoral arteries.In female WT mice, VPAC1 receptors appear to play a dominant role in PACAP-induced vasorelaxation both in carotid and in femoral arteries. In the PACAP KO group PAC1R activation exerts vasorelaxation in the femoral arteries but in carotid arteries there is no significant effect of the activation of this receptor. In the background of this regional difference, decreased PAC1R and increased VPAC1R availability in the carotid arteries was found. LA - English DB - MTMT ER - TY - JOUR AU - Nemerkényiné Hidegkuti, Krisztina AU - Koller, Ákos TI - Emlékezés Dr. John O. Holloszy professzorra. Remembering Dr. John O. Holloszy TS - Remembering Dr. John O. Holloszy JF - TESTNEVELÉS SPORT TUDOMÁNY / PHYSICAL EDUCATION, SPORT, SCIENCE J2 - TESTNEVELÉS SPORT TUDOMÁNY VL - 3 PY - 2018 IS - 3-4 SP - 64 EP - 65 PG - 2 SN - 2498-7646 UR - https://m2.mtmt.hu/api/publication/33192843 ID - 33192843 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Koller, Ákos AU - Nádasy, György László AU - Bednárikné Dörnyei, Gabriella AU - Szénási, Annamária AU - Szekeres, Mária TI - Négy hetes napi futás-tréning a patkány szívkoszorúserek biomechanikai és funkcionális adaptációját hozza létre JF - MAGYAR SPORTTUDOMÁNYI SZEMLE J2 - M SPORTTUD SZLE VL - 19 PY - 2018 IS - 75 SP - 55 EP - 56 PG - 2 SN - 1586-5428 UR - https://m2.mtmt.hu/api/publication/30397629 ID - 30397629 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Koller, Ákos AU - Szénási, Annamária AU - Bednárikné Dörnyei, Gabriella AU - Kovacs, N AU - Lelbach, Ádám Antal AU - Kovacs, I TI - Coronary microvascular and cardiac dysfunction due to homocysteine pathometabolism; a complex therapeutic design JF - CURRENT PHARMACEUTICAL DESIGN J2 - CURR PHARM DESIGN VL - 24 ET - 0 PY - 2018 IS - 25 SP - 2911 EP - 2920 PG - 10 SN - 1381-6128 DO - 10.2174/1381612824666180625125450 UR - https://m2.mtmt.hu/api/publication/3393140 ID - 3393140 AB - In various metabolic diseases both the coronary circulation and cardiac metabolism are altered. Here we summarize the effects of a condition called hyperhomocysteinemia (HHcy) - which can develop due to genetic or environmental causes - on the function of coronary microvessels and heart. This metabolic disease is underappreciated, yet even mild or moderate elevation of plasma concentrations of homocystein (Hcy, plasma Hcy >16 M), a sulfur-containing amino acid produced via methionine metabolism) leads to coronary and peripheral artery and even venous vessel diseases, leading to vasomotor dysfunction and increased thrombosis, consequently increased morbidity and mortality. Yet the underlying mechanisms are not yet revealed. Recent studies indicated that there are common pathomechanisms, which may affect all cellular function involved. Two main mechanisms are the dysfunction of nitric oxide (NO) pathway resulting reduced dilator responses of arteries and arterioles with methionine diet-induced hyperhomocysteinemia, and the simultaneously increased thromboxane A2 (TXA2) activity both in vessels and platelets. These changes are likely due to an increased production of reactive oxidative species (oxidative stress) due to increased NADPH oxidase assembly, which eventually lead to inflammatory process (indicated by increases in TNFalpha, NFkappabeta, p22phox, p67phox, and rac-1, levels) and changes in various gene expressions and morphological remodeling of vessels. Increased superoxide production and reduced ability of NO alters the regulation of mitochondrial function in the myocardium. The interactions of these pathomechanisms may explain why HHcy increases the uptake of glucose and lactate and decreases the uptake of free fatty acid by the heart. The pathological consequences of HHcy could be worsening by the simultaneous presence of other risk factors, such as hyperlipidemia, diabetes mellitus and metabolic syndrome. All in all, HHcy and associated pathometabolism lead to severe changes and dysfunctions of coronary arterial vessels and cardiac function, which may not always apparent in clinical settings but most likely, contribute to increased prevalence of cardiovascular diseases and mortality, which however can be reduced by appropriate prevention and treatments. We believe that HHcy is an underestimated - likely due to inappropriate clinical trials - but serious disease condition because it promotes the development of atherosclerosis in large arterial vessels, vasomotor dysfunction in microvessels, hypertension and thrombosis. In this review we will summarizes previous functional findings focusing on coronary vessels and cardiac function and the underlying cellular and molecular mechanisms enabling the development of novel treatments. LA - English DB - MTMT ER - TY - JOUR AU - Deng, W AU - Kandhi, S AU - Zhang, B AU - Huang, A AU - Koller, Ákos AU - Sun, D TI - Extravascular Blood Augments Myogenic Constriction of Cerebral Arterioles: Implications for Hemorrhage-Induced Vasospasm. JF - JOURNAL OF THE AMERICAN HEART ASSOCIATION J2 - J AM HEART ASSOC VL - 7 PY - 2018 IS - 8 PG - 12 SN - 2047-9980 DO - 10.1161/JAHA.118.008623 UR - https://m2.mtmt.hu/api/publication/3360066 ID - 3360066 N1 - Funding Agency and Grant Number: NIH [HL070653, HL129797]; National Research, Development, and Innovation Office of Hungary [OTKA K108444] Funding text: This work was supported by grants NIH HL070653 and HL129797 and in part by the National Research, Development, and Innovation Office of Hungary (OTKA K108444). AB - BACKGROUND: Subarachnoid hemorrhage is a serious clinical condition that impairs local cerebral blood flow perfusion and consequently initiates neuronal dysfunction. Pressure-sensitive myogenic vasomotor regulation is an important mechanism involved in the regulation of cerebral blood flow. We hypothesized that extravascular hemolyzed blood enhances arteriolar myogenic constriction, which in vivo may contribute to the reduction of local cerebral blood flow after subarachnoid hemorrhage. METHODS AND RESULTS: Arterioles isolated from the middle cerebral artery (MCA arterioles) of mice were cannulated in a perfusion chamber. Arteriolar diameters in response to step increases in intraluminal pressure (20-120 mm Hg) were measured in various experimental conditions. In response to increases in intraluminal pressure, all MCA arterioles exhibited myogenic vasoconstrictions. Compared with controls, the pressure-induced constriction was significantly enhanced in arterioles (in vitro) exposed to extravascular hemolyzed blood or different concentrations of extracellular erythrocyte lysate (1%, 10%, and 20%) for different exposure durations (1-6 hours). The magnitude of enhancement was proportional to the lysate concentration and exposure duration. In in vivo experiments, 10 muL of autologous blood lysate were injected into the mouse subarachnoid space on the surface of the left MCA. Two hours later, MCA arterioles were isolated and left MCA arterioles displayed enhanced myogenic responses compared with the right MCA. The enhanced myogenic response was prevented by scavenge of superoxide in both in vitro and in vivo experiments. CONCLUSIONS: Extravascular hemolyzed blood, perhaps by promoting vascular production of superoxide, augments myogenic constriction of cerebral arterioles, which plays a crucial role in the subarachnoid hemorrhage-induced cerebral ischemia. LA - English DB - MTMT ER - TY - JOUR AU - Ivic, Ivan AU - Varjú-Solymár, Margit AU - Fülöp, Balázs Dániel AU - Hashimoto, H AU - Tóth, Gábor AU - Tamás, Andrea AU - Juhász, Tamás AU - Koller, Ákos AU - Reglődi, Dóra TI - Aging-Induced Modulation of Pituitary Adenylate Cyclase-Activating Peptide- and Vasoactive Intestinal Peptide-Induced Vasomotor Responses in the Arteries of Mice JF - JOURNAL OF VASCULAR RESEARCH J2 - J VASC RES VL - 54 PY - 2017 IS - 6 SP - 359 EP - 366 PG - 8 SN - 1018-1172 DO - 10.1159/000481781 UR - https://m2.mtmt.hu/api/publication/3294542 ID - 3294542 AB - Pituitary adenylate cyclase-activating peptide (PACAP; 1-38 and 1-27) and vasoactive intestinal peptide (VIP) are related neuropeptides of the secretin/glucagon family. Overlapping signaling through G-protein-coupled receptors mediates their vasomotor activity. We previously showed that PACAP deficiency (PACAP-KO) shifts the mechanisms of vascular response and maintains arterial relaxation through the VIP backup mechanism and (mainly) its VPAC1R, but their age-dependent modulation is still unknown. We hypothesized that backup mechanisms exist, which maintain the vasomotor activity of these peptides also in older age. Thus, we investigated the effects of exogenous VIP and PACAP peptides in isolated carotid arteries of 2- and 15-month-old wild-type (WT) and PACAP-KO mice. All peptides induced relaxation in the arteries of young WT mice, whereas in young PACAP-KO mice PACAP1-27 and VIP, but not PACAP1-38, induced relaxation. Unlike VIP, PACAP-induced vasomotor responses were reduced in aging WT mice. However, in the arteries of aging PACAP-KO mice, PACAP1-27- and VIP-induced responses were reduced, but PACAP1-38 showed a greater vasomotor response compared to that of young PACAP-KO animals. There were no significant differences between the vasomotor responses of aging WT and PACAP-KO mice. Our data suggest that, in the absence of PACAP both in young and old ages, the vascular response is mediated through backup mechanisms, most likely VIP, maintaining proper vascular relaxation in aging-induced PACAP insufficiency. LA - English DB - MTMT ER - TY - JOUR AU - Kovácsné Bobály, Viktória AU - Szilágyi, Brigitta AU - Makai, Alexandra AU - Koller, Ákos AU - Járomi, Melinda TI - Új low back pain prevenciós mozgásprogram, amely javítja a törzsizmok állapotát és a lumbalis motoros kontrollt [Improvement of lumbal motor control and trunkmuscle conditions with a novel low back pain prevention exercise program] JF - ORVOSI HETILAP J2 - ORV HETIL VL - 158 PY - 2017 IS - 2 SP - 58 EP - 66 PG - 9 SN - 0030-6002 DO - 10.1556/650.2017.30640 UR - https://m2.mtmt.hu/api/publication/3145593 ID - 3145593 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Szénási, Annamária AU - Bednárikné Dörnyei, Gabriella AU - Racz, A AU - Debreczeni, Béla AU - Koller, Ákos TI - Vázizomkisvénák vazomotortónusának intrinszik szabályozómechanizmusai JF - ORVOSI HETILAP J2 - ORV HETIL VL - 157 PY - 2016 IS - 21 SP - 805 EP - 812 PG - 8 SN - 0030-6002 DO - 10.1556/650.2016.30461 UR - https://m2.mtmt.hu/api/publication/3066227 ID - 3066227 AB - In many developed countries the prevalence of venous disorders and its consequences are higher than that of arterial diseases. Thus it is very important to understand the exact physiological and pathophysiological function of small veins and their control mechanisms. Small veins and venules have an important role in the regulation of capillary fluid exchange, as well as return of the venous blood into the heart. However, there is only limited knowledge available regarding the role of local mechanisms controlling the vasomotor tone and diameter of small veins. In the last decade the authors focused on the elucidation of these mechanisms in isolated skeletal muscle venules of rats. Their results suggest that the tone of small veins is controlled by the integration of several mechanisms, activated by the intraluminal pressure and flow/wall shear stress, in addition to numerous local mediators synthesized and released from the smooth muscle and endothelium. These mechanisms are involved - in a complex manner - in the control of postcapillary resistance, thus regulation of tissue blood supply, venous return and consequently in the modulation of the cardiac output, as well. Orv. Hetil., 2016, 157(21), 805-812. LA - Hungarian DB - MTMT ER -