β1–β2 blocking activity of propranolol and metoprolol in the unanaesthetized genetically hypertensive and normotensive rat

Summary The β-antagonistic activity of propranolol and metoprolol has been evaluated, in terms of inhibition of isoproterenol effects, “in vitro” (isolated right atria and tracheae) and “in vivo” in unanaesthetized normotensive and spontaneously hypertensive rats (SHR). Metoprolol resulted 13 - 6.4 - 14 times more cardioselective than propranolol in the three aforementioned experimental models, respectively. SHR, because of its decreased baroceptor sensitivity to trigger the tachicardic reflex, proves a good model for the evaluation of β 1 antagonistic activity of “cardioselective” β-blockers, which could be underevaluated in the normotensive rat. Moreover, the agonistic activity of isoproterenol has been compared in normo and hypertensive rats in order to ascertain whether the different number of β 1 receptors in the two strains could influence the biological response to their stimulation and/or blockade.