21 research outputs found
Enantioselective pharmacokinetics and cardiovascular effects of nebivolol in L-NAME hypertensive rats
The cardiovascular effects and pharmacokinetics of nebivolol were assessed in N(G)-nitro-l-arginine methyl ester (L-NAME) hypertensive and normotensive control rats. Male Wistar rats were randomly divided to drink tap water (control) or L-NAME solution for 2 weeks. The effects of nebivolol (3 or 10âmgâkgâ1 i.v.) on blood pressure (BP), heart rate and BP variability (BPV) were recorded in awake L-NAME and control rats. Short-term and beat-to-beat BPV was assessed by the s.d. and spectral analysis of the BP recordings. Nebivolol pharmacokinetics was studied by means of traditional blood sampling. Nebivolol showed enantioselective pharmacokinetics in both experimental groups; the clearance and the volume of distribution of l-nebivolol were significantly greater than those of the d-enantiomer. The hypotensive response to nebivolol was significantly enhanced in L-NAME rats (Îmean arterial pressure (MAP): â16.1±1.1%, P<0.05 vs. control rats) compared with normotensive animals (ÎMAP: â1.4±2.1%). An analysis of the beat-to-beat BPV showed a greater reduction in VLF BPV in the L-NAME compare with the control rats. Nebivolol significantly reduced the low-frequency/high-frequency ratio in hypertensive L-NAME animals compared with normotensive rats. Short-term BPV was markedly reduced by nebivolol in both experimental groups, although the attenuation of the s.d. of BP recording was greater in L-NAME rats. In conclusion, the hypotensive efficacy of nebivolol is significantly enhanced in L-NAME rats compared with normotensive animals, which is most likely due to a greater reduction in vascular sympathetic activity. Nebivolol markedly attenuated short-term BPV in both experimental groups, suggesting that ÎČ-blockers with additional pharmacological actions provide beneficial cardiovascular effects by controlling high BP and its short-term variability.Fil: Bertera, Facundo Martin. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Departamento de FarmacologĂa; ArgentinaFil: del Mauro, Julieta SofĂa. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Departamento de FarmacologĂa; ArgentinaFil: Lovera, Valeria. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Departamento de FarmacologĂa; ArgentinaFil: Chiappetta, Diego AndrĂ©s. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Departamento de TecnologĂa FarmacĂ©utica; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Polizio, Ariel HĂ©ctor. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Departamento de FarmacologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Taira, Carlos Alberto. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Departamento de FarmacologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Höcht, Christian. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Departamento de FarmacologĂa; Argentin