Key result
Nebivolol suppresses atrial chronotropy and inotropy through nitric oxide-dependent pathways in preclinical models.
Why the study?
The study aimed to comparatively evaluate the chronotropic, inotropic, and vascular responses of propranolol, metoprolol, and nebivolol in isolated rat atria and thoracic aorta preparations based on their distinct pharmacological profiles.
p-value: p=<0.05
In isolated rat preparations, nebivolol demonstrates pronounced negative chronotropic and inotropic effects that are mediated by nitric oxide, differentiating it from propranolol and metoprolol.
Nebivolol's NO-dependent negative chronotropy in rat atria distinguishes it from other β-blockers; leaves open translation to human cardiac effects.
Background: Propranolol (a non-selective β-blocker), metoprolol (a β1-selective blocker), and nebivolol (a β1-selective blocker with nitric oxide (NO)-releasing properties) are widely used in the treatment of various cardiovascular diseases. Based on their distinct pharmacological profiles at β-adrenergic receptors, we aimed to comparatively evaluate their effects on chronotropic, inotropic, and vascular responses in isolated rat atria and thoracic aorta preparations. Methods: In this study, isolated right, left atria and thoracic aorta preparations were used and mounted in organ bath systems. The right atrium was used to assess spontaneous beating rate (chronotropic responses), whereas the left atrium was used to evaluate contractile force (inotropic responses). Cumulative concentration-response curves were obtained by administering increasing concentrations (10-9-10-5 M) of propranolol, metoprolol, and nebivolol in noradrenaline (NA)-stimulated atrial preparations. To determine the contribution of NO, nebivolol-induced negative chronotropic and inotropic responses were also examined in the presence of the NO synthase inhibitor L-NAME (10-5 M). In endothelium-intact thoracic aorta rings, NA-induced contractile responses were also evaluated in the presence of each β-blocker with different concentrations (10-7, 10-6, 10-5 M). Results: Propranolol, metoprolol, and nebivolol produced negative chronotropic and inotropic effects in a concentration-dependent manner in isolated right and left atrial preparations. The negative chronotropic and inotropic effects of nebivolol were significantly attenuated in the presence of L-NAME (P < 0.05). NA induced a concentration-dependent increase in contractile responses in endothelium-intact aortic rings. Propranolol, metoprolol, and nebivolol caused rightward shifts of the NA concentration-response curves and Schild plot analysis revealed pA2 values of 6.64 ± 0.47, 6.47 ± 0.46, and 6.95 ± 0.35, respectively. Conclusion: These findings demonstrate that propranolol, metoprolol, and nebivolol show differential pharmacological profiles affecting atrial and vascular responses under NA stimulation in isolated rat atrial and aorta preparations. Notably, NO appears to be a key mediator of nebivolol's cardiac effects, reflected in its pronounced negative chronotropic and inotropic responses in isolated atrial tissues.
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ALTUNKAYNAK-CAMCA et al. (2026) studied this question. Propranolol, metoprolol, and nebivolol vs. Baseline / L-NAME was evaluated on Chronotropic, inotropic, and vascular responses (p=<0.05). Propranolol, metoprolol, and nebivolol produced negative chronotropic and inotropic effects in isolated rat atria, with nebivolol's effects significantly attenuated by NO synthase inhibition (P < 0.05).
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