The β-adrenoceptor subtype(s) mediating adrenaline- and dobutamine-induced blood pressure and heart rate changes in healthy volunteers

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.