title: The Beta-1-Receptor Blocker Nebivolol Elicits Dilation of Cerebral Arteries by Reducing Smooth Muscle [Ca2+]i.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  Vasomotor responses were measured by videomicroscopy and the intracellular Ca2+ by the Fura-2 AM ratiometric method. Under control conditions, nebivolol elicited a substantial dilation of the BA (from 216±22 to 394±20 μm; 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 nebivolol-induced dilation. Also, the BKCa channel blocker iberiotoxin and KCa channel inhibitor TEA significantly reduced nebivolol-induced dilation. Nebivolol significantly reduced smooth muscle Ca2+ 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.
authors.affiliation: Institute for Translational Medicine and Szentagothai Research Centre, University of Pecs, Medical School, Pecs, Hungary.|Department of Central Anesthesiology and Intensive Therapy, Petz Aladar County Teaching Hospital, Gyor, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Cseplo
authors.affiliation: Institute for Translational Medicine and Szentagothai Research Centre, University of Pecs, Medical School, Pecs, Hungary.|Department of Anaesthesiology and Intensive Therapy, University of Pecs, Medical School, Pecs, Hungary.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Vamos
authors.affiliation: Institute for Translational Medicine and Szentagothai Research Centre, University of Pecs, Medical School, Pecs, Hungary.|Department of Anatomy, University of Pecs, Medical School, Pecs, Hungary.
authors.forename: Ivan
authors.initials: I
authors.lastname: Ivic
authors.affiliation: Institute for Translational Medicine and Szentagothai Research Centre, University of Pecs, Medical School, Pecs, Hungary.
authors.forename: Orsolya
authors.initials: O
authors.lastname: Torok
authors.affiliation: Institute of Cardiology, Division of Clinical Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Toth
authors.affiliation: Institute for Translational Medicine and Szentagothai Research Centre, University of Pecs, Medical School, Pecs, Hungary.|Department of Neurosurgery, University of Pecs, Medical School, Pecs, Hungary.|Department of Physiology, New York Medical College, Valhalla, New York, United States of America.|Institute of Natural Sciences, University of Physical Education, Budapest, Hungary.
authors.forename: Akos
authors.initials: A
authors.lastname: Koller
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002536:Cerebral Arteries / Q000187:drug effects* / Q000378:metabolism; D004106:Dilatation / Q000379:methods; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016257:Fura-2 / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism; D000068577:Nebivolol / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D018342:Receptors, Adrenergic, beta-1; D014665:Vasodilator Agents; D000068577:Nebivolol; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D002118:Calcium; D016257:Fura-2; D019331:NG-Nitroarginine Methyl Ester