Nebivolol reduces intracellular Ca2+ and elicits dilations in isolated rat basilar arteries (1070.7)

Abstract

Experimental and clinical studies have revealed that the antiarrhythmic and antihypertensive, highly selective β1‐adrenerg receptor blocker, nebivolol elicits dilations in peripheral arteries, in which a role for nitric oxide (NO) has been implicated. However, its effect on the diameter of cerebral vessels has not been investigated. We hypothesized that nebivolol increases the diameter of isolated cerebral arteries.Basilar arteries (BA) were isolated from male Wistar rats and were mounted into isotonic myograph chamber. Diameters of vessels were measured by video‐microscopy in response to vasoactive agents, and the intravascular Ca2+ changes was detected by the fura‐2 ratiometric method.Nebivolol elicited significant vasodilation, despite the presence of L‐NAME (NOS inhibitor) or ODQ (guanylate cyclase blocker) or SQ22536 (adenylyl cyclase blocker). Nebivolol significantly reduced the ratiometric calcium‐signal that correlated with changes in diameter.In isolated BA nebivolol: 1) elicits significant dilation, 2) to which NO‐cGMP/cAMP pathway does not contribute significantly, 3) decreases vascular wall [Ca2+]i. (Supported by: OTKA K108444, SROP‐4.2.2.A‐11/1/KONV‐2012‐0024, SROP‐4.2.2.A‐11/1/KONV‐2012‐0017, TAMOP 4.2.4.A/2‐11‐1‐2012‐0001 “National Excellence Program”)Grant Funding Source: OTKA K108444, TAMOP 4.2.4.A/2‐11‐1‐2012‐0001 „National Excellence Program”