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The Beta-1-Receptor Blocker Nebivolol Elicits Dilation of Cerebral Arteries by Reducing Smooth Muscle [Ca2+]i.
- Source :
-
PloS one [PLoS One] 2016 Oct 07; Vol. 11 (10), pp. e0164010. Date of Electronic Publication: 2016 Oct 07 (Print Publication: 2016). - Publication Year :
- 2016
-
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.<br />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.<br />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.<br />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.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Animals
Cerebral Arteries metabolism
Dilatation methods
Endothelium, Vascular metabolism
Enzyme Inhibitors pharmacology
Fura-2 metabolism
Guanylate Cyclase metabolism
Male
Muscle, Smooth, Vascular metabolism
NG-Nitroarginine Methyl Ester metabolism
Nitric Oxide metabolism
Nitric Oxide Synthase metabolism
Potassium Channel Blockers pharmacology
Rats
Rats, Wistar
Receptors, Adrenergic, beta-1 metabolism
Vasoconstriction drug effects
Vasodilator Agents pharmacology
Adrenergic beta-1 Receptor Antagonists pharmacology
Calcium metabolism
Cerebral Arteries drug effects
Endothelium, Vascular drug effects
Muscle, Smooth, Vascular drug effects
Nebivolol pharmacology
Vasodilation drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 11
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 27716772
- Full Text :
- https://doi.org/10.1371/journal.pone.0164010