In vivo and in vitro pharmacodynamic properties of metoprolol in aortic coarctated rats.
The chronotropic effects of metoprolol (MP) in vivo after intravenous administration and in vitro in isolated atria of aortic coarctated rats were studied. MP levels in arterial dialysates and changes in arterial pressure and heart rate (HR) were determined after intravenous administration of MP. Affinity of MP by means of shifting of noradrenaline concentration-response curve and the inverse agonist activity of MP were studied in isolated atria. The IC(50) value of MP cardiac effect was smaller in aortic coarctated rats (13.0+/-5.4 ng ml(-1), n=5) than in sham operated (SO) rats (36.2+/-4.6 ng ml(-1), n=5). In isolated atria, no difference was found in MP dissociation constant and its inverse agonist activity between both experimental groups. In conclusion, the affinity and inverse agonism activity of MP would not be altered in aortic coarctated rats. A greater sensibility to the chronotropic effect of MP was found in coarctated rats.
Höcht
Christian
C
Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Junín 956, (C1113AAD)Buenos Aires, Argentina. chocht@ffyb.uba.ar
Di Verniero
Carla
C
Opezzo
Javier A W
JA
Taira
Carlos A
CA
D000818:Animals; D001017:Aortic Coarctation / Q000150:complications / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology*; D066298:In Vitro Techniques; D008790:Metoprolol / Q000008:administration & dosage / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D012044:Regression Analysis; D013997:Time Factors
D011943:Receptors, Adrenergic, beta; D008790:Metoprolol; D009638:Norepinephrine