TY - JOUR AU - Hricisák, László AU - Pál, Éva AU - Nagy, Dorina AU - Delank, Max AU - Polycarpou, Andreas AU - Fülöp, Ágnes AU - Sándor, Péter AU - Sótonyi, Péter AU - Ungvári, Zoltán István AU - Benyó, Zoltán TI - NO Deficiency Compromises Inter- and Intrahemispheric Blood Flow Adaptation to Unilateral Carotid Artery Occlusion JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 2 PG - 17 SN - 1661-6596 DO - 10.3390/ijms25020697 UR - https://m2.mtmt.hu/api/publication/34482135 ID - 34482135 N1 - I AB - Carotid artery stenosis (CAS) affects approximately 5–7.5% of older adults and is recognized as a significant risk factor for vascular cognitive impairment (VCI). The impact of CAS on cerebral blood flow (CBF) within the ipsilateral hemisphere relies on the adaptive capabilities of the cerebral microcirculation. In this study, we aimed to test the hypothesis that the impaired availability of nitric oxide (NO) compromises CBF homeostasis after unilateral carotid artery occlusion (CAO). To investigate this, three mouse models exhibiting compromised production of NO were tested: NOS1 knockout, NOS1/3 double knockout, and mice treated with the NO synthesis inhibitor L-NAME. Regional CBF changes following CAO were evaluated using laser-speckle contrast imaging (LSCI). Our findings demonstrated that NOS1 knockout, NOS1/3 double knockout, and L-NAME-treated mice exhibited impaired CBF adaptation to CAO. Furthermore, genetic deficiency of one or two NO synthase isoforms increased the tortuosity of pial collaterals connecting the frontoparietal and temporal regions. In conclusion, our study highlights the significant contribution of NO production to the functional adaptation of cerebrocortical microcirculation to unilateral CAO. We propose that impaired bioavailability of NO contributes to the impaired CBF homeostasis by altering inter- and intrahemispheric blood flow redistribution after unilateral disruption of carotid artery flow. LA - English DB - MTMT ER - TY - JOUR AU - Pál, Éva AU - Hricisák, László AU - Lékai, Á. AU - Nagy, Dorina AU - Fülöp, Ágnes AU - Erben, R.G. AU - Várbíró, Szabolcs AU - Sándor, Péter AU - Benyó, Zoltán TI - Ablation of Vitamin D Signaling Compromises Cerebrovascular Adaptation to Carotid Artery Occlusion in Mice JF - CELLS J2 - CELLS-BASEL VL - 9 PY - 2020 IS - 6 PG - 17 SN - 2073-4409 DO - 10.3390/cells9061457 UR - https://m2.mtmt.hu/api/publication/31365424 ID - 31365424 LA - English DB - MTMT ER - TY - GEN AU - Hricisák, László AU - Simoes, Dobrydnio L AU - Jabronka, N AU - Portörő-Gál, P AU - Janovicz, Anna AU - Polycarpou, A AU - Ruisanchez, Éva AU - Sándor, Péter AU - Benyó, Zoltán TI - NOS izoenzimek szerepe az egér agykérgi váráramlásának szabályozásában PY - 2018 UR - https://m2.mtmt.hu/api/publication/30519748 ID - 30519748 LA - Hungarian DB - MTMT ER - TY - GEN AU - Hricisák, László AU - Polycarpou, A AU - Iring, András AU - Safar, D AU - Ruisanchez, Éva AU - Horváth, Béla András AU - Sándor, Péter AU - Benyó, Zoltán TI - A NITROGÉN-MONOXID SZEREPE A REGIONÁLIS AGYKÉRGI VÉRÁRAMLÁS SZABÁLYOZÁSÁBAN FÉLOLDALI ARTERIA CAROTIS ELZÁRÁS UTÁN PY - 2017 PG - 1 UR - https://m2.mtmt.hu/api/publication/3243370 ID - 3243370 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Polycarpou, A AU - Hricisák, László AU - Iring, András AU - Safar, D AU - Ruisanchez, Éva AU - Horváth, Béla András AU - Sándor, Péter AU - Benyó, Zoltán TI - Adaptation of the Cerebrocortical Circulation to Carotid Artery Occlusion Involves Blood Flow Redistribution between Cortical Regions and is Independent of eNOS JF - AMERICAN JOURNAL OF PHYSIOLOGY: HEART AND CIRCULATORY PHYSIOLOGY J2 - AM J PHYSIOL HEART C VL - 311 PY - 2016 IS - 4 SP - H972 EP - H980 SN - 0363-6135 DO - 10.1152/ajpheart.00197.2016 UR - https://m2.mtmt.hu/api/publication/3100748 ID - 3100748 N1 - Institute of Clinical Experimental Research, Semmelweis University, Budapest, Hungary Max Planck Institute for Heart and Lung Research, Department of Pharmacology, Bad Nauheim, Germany Cited By :10 Export Date: 13 January 2024 CODEN: AJPPD Correspondence Address: Benyó, Z.; Institute of Clinical Experimental Research, Tű u. 37-47, Hungary; email: benyo.zoltan@med.semmelweis-univ.hu AB - Cerebral circulation is secured by feed-forward and feed-back control pathways to maintain and eventually reestablish the optimal oxygen and nutrient supply of neurons in case of disturbances of the cardiovascular system. Using the high temporal and spatial resolution of laser-speckle imaging we aimed to analyze the pattern of cerebrocortical blood flow (CoBF) changes after unilateral (left) carotid artery occlusion (CAO) in anesthetized mice in order to evaluate the contribution of macrovascular (Willis circle) vs. pial collateral vessels as well as that of endothelial nitric oxide synthase (eNOS) to the cerebrovascular adaptation to CAO. In wild-type mice CoBF reduction in the left temporal cortex started immediately after CAO, reaching its maximum (-26%) at 5-10 s. Thereafter, CoBF recovered close to the pre-occlusion level within 30 s indicating the activation of feed-back pathway(s). Interestingly, the frontoparietal cerebrocortical regions also showed CoBF reduction in the left (-17-19%) but not in the right hemisphere, although these brain areas receive their blood supply from the common azygos anterior cerebral artery in mice. In eNOS-deficient animals the acute CoBF reduction after CAO was unaltered, and the recovery was even accelerated as compared to controls. These results indicate that (i) the Willis circle alone is not sufficient to provide an immediate compensation for the loss of one carotid artery, (ii) pial collaterals attenuate the ischemia of the temporal cortex ipsilateral to CAO at the expense of the blood supply of the frontoparietal region, and (iii) eNOS, surprisingly, does not play an important role in this CoBF redistribution. LA - English DB - MTMT ER - TY - BOOK AU - Sándor, Péter AU - Benyó, Zoltán TI - Az agyi vérkeringés élettani alapjai: önszabályozó mechanizmusok ET - 0 PB - Semmelweis Kiadó és Multimédia Stúdió CY - Budapest PY - 2016 SP - 134 SN - 9789633313756 UR - https://m2.mtmt.hu/api/publication/3013894 ID - 3013894 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Benyó, Zoltán AU - Ruisanchez, Éva AU - Leszl-Ishiguro, Mirjam AU - Sándor, Péter AU - Pacher, Pál TI - Endocannabinoids in Cerebrovascular Regulation JF - AMERICAN JOURNAL OF PHYSIOLOGY: HEART AND CIRCULATORY PHYSIOLOGY J2 - AM J PHYSIOL HEART C VL - 310 PY - 2016 IS - 7 SP - H785 EP - H801 SN - 0363-6135 DO - 10.1152/ajpheart.00571.2015 UR - https://m2.mtmt.hu/api/publication/3011598 ID - 3011598 N1 - Institute of Clinical Experimental Research, Semmelweis University, Budapest, Hungary Laboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, United States Cited By :62 Export Date: 13 January 2024 CODEN: AJPPD Correspondence Address: Benyó, Z.; Institute of Clinical Experimental Research, Tűzoltó u. 37-47, Hungary; email: benyo.zoltan@med.semmelweis-univ.hu AB - The cerebral blood flow (CBF) is tightly regulated by myogenic, endothelial, metabolic and neural mechanisms under physiological conditions, and a large body of recent evidence indicates that inflammatory pathways have a major influence on the cerebral blood perfusion in certain CNS disorders, like hemorrhagic and ischemic stroke, traumatic brain injury and vascular dementia. All major cell types involved in cerebrovascular control pathways (i.e. smooth muscle, endothelium, neurons, astrocytes, pericytes, microglia and leukocytes) are capable of synthesizing endocannabinoids and/or express some or several of their target proteins (i.e. the cannabinoid 1 and 2 receptors (CB1 and CB2) and the TRPV1 ion channel). Therefore, the endocannabinoid system may importantly modulate the regulation of cerebral circulation under physiological and pathophysiological conditions in a very complex manner. Experimental data accumulated since the late 1990s indicate that the direct effect of cannabinoids on cerebral vessels is vasodilation mediated, at least in part, by CB1 receptors. Cannabinoid-induced cerebrovascular relaxation involves both a direct inhibition of smooth muscle contractility and a release of vasodilator mediator(s) from the endothelium. However, under stress conditions (e.g. in conscious restrained animals or during hypoxia and hypercapnia) cannabinoid receptor activation was shown to induce a reduction of the CBF, probably via inhibition of the electrical and/or metabolic activity of neurons. Finally, in certain cerebrovascular pathologies (e.g. subarachnoid hemorrhage as well as traumatic and ischemic brain injury) activation of CB2 (and probably yet unidentified non-CB1/non-CB2) receptors appear to improve the blood perfusion of the brain via attenuating vascular inflammation. LA - English DB - MTMT ER - TY - GEN AU - Benyó, Zoltán AU - Ruisanchez, Éva AU - Iring, András AU - Leszl-Ishiguro, Miriam AU - Sándor, Péter AU - Pacher, Pál TI - Endocannabinoidok szerepe az agyi vérkeringés szabályozásában PY - 2015 UR - https://m2.mtmt.hu/api/publication/30792746 ID - 30792746 LA - Hungarian DB - MTMT ER - TY - CHAP AU - Sándor, Péter ED - Nagy, Zoltán TI - Az agyi vérellátás szabályozása. A mikrokeringés regulációjának fő tényezői. T2 - Vascularis neurológia PB - Semmelweis Kiadó CY - Budapest SN - 9789633310168 PY - 2015 SP - 15 EP - 30 PG - 16 UR - https://m2.mtmt.hu/api/publication/3063231 ID - 3063231 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Iring, András AU - Ruisanchez, Éva AU - Leszl-Ishiguro, Mirjam AU - Horváth, Béla András AU - Benkő, Rita AU - Lacza, Zsombor AU - Járai, Zoltán AU - Sándor, Péter AU - Di Marzo, V AU - Pacher, Pál AU - Benyó, Zoltán TI - Role of endocannabinoids and cannabinoid-1 receptors in cerebrocortical blood flow regulation JF - PLOS ONE J2 - PLOS ONE VL - 8 PY - 2013 IS - 1 PG - 11 SN - 1932-6203 DO - 10.1371/journal.pone.0053390 UR - https://m2.mtmt.hu/api/publication/2181946 ID - 2181946 N1 - Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, Budapest, Hungary Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, United States Department of Cardiology, St. Imre Teaching Hospital, Budapest, Hungary Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Naples, Italy National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, United States Cited By :22 Export Date: 1 February 2024 Correspondence Address: Benyó, Z.; Institute of Human Physiology and Clinical Experimental Research, , Budapest, Hungary; email: benyo.zoltan@med.semmelweis-univ.hu Chemicals/CAS: 1 (2,4 dichlorophenyl) 5 (4 iodophenyl) 4 methyl n (1 piperidyl) 1h pyrazole 3 carboxamide, 183232-66-8; n (4 hydroxyphenyl)arachidonamide, 183718-77-6, 198022-70-7; AM 251; Arachidonic Acids; Endocannabinoids; N-(4-hydroxyphenyl)arachidonylamide; Piperidines; Pyrazoles; Receptor, Cannabinoid, CB1 Funding details: National Institute on Alcohol Abuse and Alcoholism, NIAAA, ZIAAA000375 AB - BACKGROUND: Endocannabinoids are among the most intensively studied lipid mediators of cardiovascular functions. In the present study the effects of decreased and increased activity of the endocannabinoid system (achieved by cannabinoid-1 (CB1) receptor blockade and inhibition of cannabinoid reuptake, respectively) on the systemic and cerebral circulation were analyzed under steady-state physiological conditions and during hypoxia and hypercapnia (H/H). METHODOLOGY/PRINCIPAL FINDINGS: In anesthetized spontaneously ventilating rats the CB1-receptor antagonist/inverse agonist AM-251 (10 mg/kg, i.v.) failed to influence blood pressure (BP), cerebrocortical blood flow (CoBF, measured by laser-Doppler flowmetry) or arterial blood gas levels. In contrast, the putative cannabinoid reuptake inhibitor AM-404 (10 mg/kg, i.v.) induced triphasic responses, some of which could be blocked by AM-251. Hypertension during phase I was resistant to AM-251, whereas the concomitant CoBF-increase was attenuated. In contrast, hypotension during phase III was sensitive to AM-251, whereas the concomitant CoBF-decrease was not. Therefore, CoBF autoregulation appeared to shift towards higher BP levels after CB1-blockade. During phase II H/H developed due to respiratory depression, which could be inhibited by AM-251. Interestingly, however, the concomitant rise in CoBF remained unchanged after AM-251, indicating that CB1-blockade potentially enhanced the reactivity of the CoBF to H/H. In accordance with this hypothesis, AM-251 induced a significant enhancement of the CoBF responses during controlled stepwise H/H. CONCLUSION/SIGNIFICANCE: Under resting physiological conditions CB1-receptor mediated mechanisms appear to have limited influence on systemic or cerebral circulation. Enhancement of endocannabinoid levels, however, induces transient CB1-independent hypertension and sustained CB1-mediated hypotension. Furthermore, enhanced endocannabinoid activity results in respiratory depression in a CB1-dependent manner. Finally, our data indicate for the first time the involvement of the endocannabinoid system and CB1-receptors in the regulation of the cerebral circulation during H/H and also raise the possibility of their contribution to the autoregulation of CoBF. LA - English DB - MTMT ER -