Cardiovascular Effects of Beta-Blockers with and without Intrinsic Sympathomimetic Activity

Abstract

Background: Celiprolol, a newer beta-blocking agent, has been reported to have vasodilatory capacity which may be due to partial beta-2-receptor agonistic activity or to alpha-receptor antagonistic or central sympathoinhibitory effects. Methods: To more critically assess the physiologic effects of celiprolol, we measured sympathetic nerve activity to muscle (MSNA), forearm blood flow (FBF), blood pressure (BP), central venous pressure, and heart rate (HR) in 10 normal volunteers at rest, during unloading of cardiopulmonary baroreceptors with lower body negative pressure (LBNP), and during a cold pressor test (CPT). Responses were compared with those seen with metoprolol and with placebo, i.e. each subject was studied three times. Results: Celiprolol did not alter resting levels of hemodynamics, FBF, and MSNA nor did it alter responses to LBNP or the CPT. In contrast, metoprolol produced significant decreases of FBF and HR, and increases of forearm vascular resistance and BP, but had also no effect on responses to the applied stress tests. Conclusions: The lack of peripheral vasoconstriction seen after acute administration of celiprolol is most likely due to its partial beta-2-receptor agonistic effect and does not seem to be due to a central or reflex action or to an alpha-blocking effect. Both beta-blockers do not impair fundamental neural mechanisms involved in circulatory homeostasis.

Optogenetic techniques for the study of native potassium channels

“…However, the number of photoswitchable proteins is rapidly increasing and for many membrane proteins trafficking mutants have been identified. For example, forward trafficking signals which may be mutated to prevent trafficking to the plasma membrane which can be rescued by WT subunits have been described for several proteins including the potassium channels Kir1.1 (Heusser et al, 2002), Kir2.1 (Ma et al, 2001), Kir3.2 (Ma and Jan, 2002), Kir3.4 (Ma and Jan, 2002), TASK1 (Girard et al, 2002), and TASK3 (Zuzarte et al, 2007). Interestingly, the strategy to rescue trafficking of one subunit by another is commonly used in nature to ensure that only heteromeric assemblies of a particular protein reach the cell surface.…”

Acute effects of beta-blocker with intrinsic sympathomimetic activity on stress-induced cardiac dysfunction in rats

“…In contrast, metoprolol produced significant decreases in forearm blood flow and heart rate, and increases in forearm vascular resistance and blood pressure. And they concluded that the lack of peripheral vasoconstriction seen after acute administration of celiprolol is most likely due to its partial ␤2-receptor agonistic effect [21]. Kobayashi et al reported that celiprolol administration resulted in a significant improvement in cardiovascular remodeling and suppression of transforming growth factor-␤1 gene expression.…”