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Effect of nebivolol on beat-to-beat and short-term blood pressure variability in spontaneously hypertensive rats

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Abstract

Cardiovascular effects and pharmacokinetics of nebivolol were assessed in spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) animals. Male SH and WKY rats were treated with vehicle or nebivolol 0.3, 3, or 10 mg kg−1 (i.v.) and effects on blood pressure (BP), heart rate, and blood pressure variability (BPV) were recorded. Plasma pharmacokinetics of d- and l-nebivolol was studied by traditional blood sampling. Short-term and beat-to-beat BPV was assessed by standard deviation and spectral analysis of BP recording, respectively. Nebivolol showed enantioselective pharmacokinetics in both experimental groups; clearance of l-nebivolol was significantly greater than d-enantiomer. Clearance of nebivolol was significantly reduced in SHR with regards to WKY animals. Hypotensive response to nebivolol 3 and 10 mg kg−1 was significantly enhanced in SHR compared with normotensive animals. Spectral analysis of beat-to-beat BPV showed a greater reduction in low frequency BPV in SHR than in WKY rats. Nebivolol 3 and 10 mg kg−1 significantly reduced ratio low frequency/high frequency BPV only in SHR. Short-term BPV was markedly reduced by nebivolol 0.3, 3, and 10 mg kg−1 in WKY and SHR. In conclusion, the hypertensive stage in SHR modifies nebivolol pharmacokinetic properties and enhances its hypotensive response due to a greater attenuation in vascular sympathetic activity and enhancement of endothelial-derived NO activity. Nebivolol markedly attenuates short-term BPV in both experimental groups providing beneficial cardiovascular effects by both controlling high blood pressure and its short-term variability.

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Acknowledgments

This work was supported by grants from Secretaría de Ciencia y Técnica, Universidad de Buenos Aires, Argentina and from the Agencia Nacional de Promoción Científica (Préstamo BID PICT 00994). Diego Chiappetta, Ariel H. Polizio, and Carlos A. Taira are Career Investigators from CONICET, Argentina.

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Authors and Affiliations

  1. Department of Pharmacology, School of Pharmacy and Biochemistry, University of Buenos Aires, Junín 956, C1113AAD, Buenos Aires, Argentina

    Facundo Martín Bertera, Julieta Sofía Del Mauro, Ariel Héctor Polizio, Carlos Alberto Taira & Christian Höcht

  2. Institute of Physiopathology and Clinical Biochemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina

    Facundo Martín Bertera, Carlos Alberto Taira & Christian Höcht

  3. Department of Pharmaceutical Technology, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina

    Diego Chiappetta

Authors
  1. Facundo Martín Bertera
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  2. Julieta Sofía Del Mauro
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  3. Ariel Héctor Polizio
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  4. Diego Chiappetta
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  5. Carlos Alberto Taira
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  6. Christian Höcht
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Correspondence to Facundo Martín Bertera.

Additional information

F. M. Bertera and J. S. Del Mauro equally contributed to this work.

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Bertera, F.M., Del Mauro, J.S., Polizio, A.H. et al. Effect of nebivolol on beat-to-beat and short-term blood pressure variability in spontaneously hypertensive rats. Naunyn-Schmiedeberg's Arch Pharmacol 385, 833–843 (2012). https://doi.org/10.1007/s00210-012-0756-9

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  • DOI: https://doi.org/10.1007/s00210-012-0756-9

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