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Nebivolol is more effective than atenolol for blood pressure variability attenuation and target organ damage prevention in L-NAME hypertensive rats

Hypertension Research volume 44, pages 791–802 (2021)Cite this article

Abstract

β-Adrenergic blockers are no longer recommended as first-line therapy due to the reduced cardioprotection of traditional β-blockers compared with other antihypertensive drugs. It is unknown whether third-generation β-blockers share the limitations of traditional β-blockers. The aim of the present study was to compare the effects of nebivolol or atenolol on central and peripheral systolic blood pressure (SBP) and its variability and target organ damage (TOD) in N-nitro-L-arginine methyl ester (L-NAME) hypertensive rats. Male Wistar rats were treated with L-NAME for 8 weeks together with oral administration of nebivolol 30 mg/kg (n = 8), atenolol 90 mg/kg (n = 8), or vehicle (n = 8). The control group was composed of vehicle-treated Wistar rats. SBP and its variability, as well as echocardiographic parameters, were assessed during the last 2 weeks of treatment. Tissue levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and transforming growth factor β (TGF-β), and histopathological parameters were evaluated in the left ventricle and aorta. Nebivolol had a greater ability than atenolol to decrease central SBP and mid-term and short-term blood pressure variability (BPV) in L-NAME rats. Echocardiographic analysis showed that nebivolol was more effective than atenolol on E/A wave ratio normalization. Compared with atenolol treatment, nebivolol had a greater protective effect on different TOD markers, inducing a decrease in collagen deposition and a reduction in the proinflammatory cytokines IL-6 and TNF-α in the left ventricle and aorta. Our findings suggest that the adverse hemodynamic profile and the reduced cardiovascular protection reported with traditional β-blockers must not be carried forward to third-generation β-blockers.

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Acknowledgements

This work was supported by grants from Secretaría de Ciencia y Técnica, Universidad de Buenos Aires [Grant Number: 20020150100142BA]. DAC, MD, AHP, GB, GEG, MAM, CAT, AC, and AHP are Career Investigators from Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.

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Authors and Affiliations

  1. Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Farmacología, Buenos Aires, Argentina

    Julieta S. Del Mauro, Yanina Santander Plantamura, Miguel A. Allo, Luciano Parola, Facundo M. Bertera, Andrea Carranza, Carlos A. Taira, Ariel H. Polizio & Christian Höcht

  2. Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Físicoquímica, Instituto de Bioquímica y Medicina Molecular (IBIMOL), Buenos Aires, Argentina

    Paula D. Prince

  3. Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Bioquímica Clínica, Laboratorio de Lípidos y Aterosclerosis, Buenos Aires, Argentina

    Nahuel Fernandez Machulsky & Gabriela Berg

  4. Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Fisiopatología y Bioquímica Clínica (INFIBIOC), Buenos Aires, Argentina

    Nahuel Fernandez Machulsky, Facundo M. Bertera, Gabriela Berg, Carlos A. Taira & Christian Höcht

  5. Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Tecnología Farmacéutica, Buenos Aires, Argentina

    Marcela A. Morettón & Diego A. Chiappetta

  6. Universidad de Buenos Aires, Facultad de Medicina, Instituto de Fisiopatología Cardiovascular (INFICA), Departamento de Patología, Buenos Aires, Argentina

    Eliana P. Bin & Martín Donato

  7. Instituto de Investigaciones Biomédicas (BIOMED UCA-CONICET), Laboratorio de Patología Cardiovascular Experimental e Hipertensión Arterial, Buenos Aires, Argentina

    Germán E. González

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  1. Julieta S. Del Mauro
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Del Mauro, J.S., Prince, P.D., Santander Plantamura, Y. et al. Nebivolol is more effective than atenolol for blood pressure variability attenuation and target organ damage prevention in L-NAME hypertensive rats. Hypertens Res 44, 791–802 (2021). https://doi.org/10.1038/s41440-021-00630-4

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