title: Effect of nebivolol on beat-to-beat and short-term blood pressure variability in spontaneously hypertensive rats.
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.
authors.affiliation: Department of Pharmacology, School of Pharmacy and Biochemistry, University of Buenos Aires, Junín 956, C1113AAD Buenos Aires, Argentina. fbertera@ffyb.uba.ar
authors.forename: Facundo Martín
authors.initials: FM
authors.lastname: Bertera
authors.forename: Julieta Sofía
authors.initials: JS
authors.lastname: Del Mauro
authors.forename: Ariel Héctor
authors.initials: AH
authors.lastname: Polizio
authors.forename: Diego
authors.initials: D
authors.lastname: Chiappetta
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Taira
authors.forename: Christian
authors.initials: C
authors.lastname: Höcht
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D001578:Benzopyrans / Q000493:pharmacokinetics / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002626:Chemistry, Pharmaceutical; D004983:Ethanolamines / Q000493:pharmacokinetics / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology; D007275:Injections, Intravenous; D008297:Male; D000068577:Nebivolol; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013237:Stereoisomerism
chemical_list: D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D001578:Benzopyrans; D004983:Ethanolamines; D000068577:Nebivolol