In order to characterize the β-adrenoceptor subtype(s) mediating blood pressure and heart rate changes induced by adrenaline and dobutamine, we compared the effects in healthy male volunteers of propranolol (5 mg i.v.) and of the β1-adrenoceptor selective antagonist bisoprolol (15 mg p.o.) on adrenaline- and dobutamine-infusion induced changes in systolic (P(syst) and diastolic blood pressure (P(diast)) and heart rate with those on blood pressure and heart rate (HR) changes induced by 'pure' α- or β-adrenoceptor agonists (phenylephrine, selective α, terbutaline, selective β2, isoprenaline, non-selective β1 and β2) Both β-adrenoceptor antagonists did not affect phenylephrine (0.25 -1.0 μg/kg/min for 10 min) infusion induced P(syst)- and P(diast)increases and HR-decreases. On the other hand, propranolol completely suppressed terbutaline (25-150 ng/kg/min for 15 min) and isoprenaline (3.5-35 ng/kg/min for 8 min) infusion induced P(syst)- and HR-increases and P(diast)-decreases while bisoprolol significantly attenuated only isoprenaline-effects but had nearly no effect on terbutaline effects. Thus, in these doses bisoprolol antagonized only β1-adrenoceptor mediated effects, propranolol both β1- and β2-adrenoceptor mediated effects, but both antagonists had no α-adrenoceptor antagonistic effects. Dobutamine (1.0-6.0 ng/kg/min for 15 min) infusion significantly increased P(syst), but did not significantly affect P(diast) and HR; bisoprolol markedly reduced dobutamine-induced P(syst)-increase. In the presence of propranolol, however, dobutamine caused P(syst)- and P(diast)-increases and HR-decreases. Adrenaline (20-120 ng/kg/min for 15 min) infusion increased P(syst) and HR and decreased P(diast). Bisoprolol did not affect P(syst)- and HR-increases, but significantly attenuated P(diast)-decreases. Adrenaline-induced tachycardia was only antagonized by bisoprolol in a dose (30 mg p.o) that had partially lost its β1-adrenoceptor selectivity. On the other hand, in the presence of propranolol adrenaline increased P(syst) and P(diast) and decreased HR. We conclude that, in healthy male volunteers, adrenaline evokes its effects on P(syst) and P(diast) through activation of β1-β2- and α-adrenoceptors, whereby in the absence of β1-adrenoceptor antagonists β1- and β2-adrenoceptors predominate; adrenaline-induced tachycardia, however, is brought about predominantly through stimulation of (cardiac) β2-adrenoceptors; dobutamine evokes its hemodynamic effects mainly via β1-adrenoceptor stimulation, however, a weak β2-adrenoceptor agonistic component appears to contribute to its effects. In addition, dobutamine exhibits α-adrenoceptor-agonistic effects that can be unmasked by β1- and β2-adrenoceptor blockade.
|Number of pages||9|
|Journal||International journal of clinical pharmacology and therapeutics|
|Publication status||Published - 10 Apr 1995|
- Heart rate
- Human cardiac β-adrenoceptors