Tags

Type your tag names separated by a space and hit enter

The Beta-1-Receptor Blocker Nebivolol Elicits Dilation of Cerebral Arteries by Reducing Smooth Muscle [Ca2+]i.
PLoS One. 2016; 11(10):e0164010.Plos

Abstract

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 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+Show Affiliations

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.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.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.Institute for Translational Medicine and Szentagothai Research Centre, University of Pecs, Medical School, Pecs, Hungary.Institute of Cardiology, Division of Clinical Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27716772

Citation

Cseplo, Peter, et al. "The Beta-1-Receptor Blocker Nebivolol Elicits Dilation of Cerebral Arteries By Reducing Smooth Muscle [Ca2+]i." PloS One, vol. 11, no. 10, 2016, pp. e0164010.
Cseplo P, Vamos Z, Ivic I, et al. The Beta-1-Receptor Blocker Nebivolol Elicits Dilation of Cerebral Arteries by Reducing Smooth Muscle [Ca2+]i. PLoS One. 2016;11(10):e0164010.
Cseplo, P., Vamos, Z., Ivic, I., Torok, O., Toth, A., & Koller, A. (2016). The Beta-1-Receptor Blocker Nebivolol Elicits Dilation of Cerebral Arteries by Reducing Smooth Muscle [Ca2+]i. PloS One, 11(10), e0164010. https://doi.org/10.1371/journal.pone.0164010
Cseplo P, et al. The Beta-1-Receptor Blocker Nebivolol Elicits Dilation of Cerebral Arteries By Reducing Smooth Muscle [Ca2+]i. PLoS One. 2016;11(10):e0164010. PubMed PMID: 27716772.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Beta-1-Receptor Blocker Nebivolol Elicits Dilation of Cerebral Arteries by Reducing Smooth Muscle [Ca2+]i. AU - Cseplo,Peter, AU - Vamos,Zoltan, AU - Ivic,Ivan, AU - Torok,Orsolya, AU - Toth,Attila, AU - Koller,Akos, Y1 - 2016/10/07/ PY - 2015/12/20/received PY - 2016/09/19/accepted PY - 2016/10/8/entrez PY - 2016/10/8/pubmed PY - 2017/6/21/medline SP - e0164010 EP - e0164010 JF - PloS one JO - PLoS One VL - 11 IS - 10 N2 - 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 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/27716772/The_Beta_1_Receptor_Blocker_Nebivolol_Elicits_Dilation_of_Cerebral_Arteries_by_Reducing_Smooth_Muscle_[Ca2+]i_ L2 - https://dx.plos.org/10.1371/journal.pone.0164010 DB - PRIME DP - Unbound Medicine ER -