Influence of adrenoceptor and muscarinic receptor blockade on the cardiovascular effects of exogenous noradrenaline and of endogenous noradrenaline released by infused tyramine

This study aimed firstly to compare the in vivo cardiovascular effects of exogenously administered and of endogenously released noradrenaline; secondly to characterize the adrenoceptors mediating these responses; thirdly to assess the influence of parasympathetic tone on the cardiovascular effects of noradrenaline. In two randomised placebo-controlled studies, healthy, young, male volunteers received intravenous (i.v.) infusions of noradrenaline at six incremental doses of 10-160 ng/kg/min and - in order to release endogenous noradrenaline - tyramine at four incremental doses of 5-20 mu g/kg/min. Noradrenaline and tyramine were administered in the absence and presence of alpha(1)-adrenoceptor blockade with doxazosin (2 mg p.o.), alpha(2)-adrenoceptor blockade with yohimbine (15 mg p.o.), selective beta(1)-adrenoceptor blockade with bisoprolol (15 mg p.o.) and muscarinic receptor blockade with atropine (15 mu g/kg i.v. loading dose followed by 0.15 mu g/kg/min by i.v. infusion). Vasoconstrictor effects were assessed by measurement of diastolic blood pressure (P-diast) and myocardial effects by measurement of systolic time intervals, namely the duration of electromechanical systole corrected for heart rate (QS(2)c). I.v. noradrenaline increased P-diast (Delta max 17 mmHg) and this was nearly completely suppressed by doxazosin but only slightly blunted by yohimbine. Noradrenaline also slightly shortened QS(2)c (Delta max -22 ms), and this was potentiated by both doxazosin and yohimbine and completely blocked by bisoprolol. I.v. tyramine reduced P-diast (Delta max -7 mmHg), which was not affected by alpha(1)-adrenoceptor blockade, and profoundly shortened QS(2)c (Delta max -104 ms) which was significantly correlated with a marked increase in systolic blood pressure (P-syst) (Delta max 57 mmHg). The shortening of QS(2)c and the rise in P-syst were not influenced by alpha-adrenoceptor blockade but were antagonized by bisoprolol. Atropine potentiated the blood pressure rise and the shortening of QS(2)c induced by i.v. noradrenaline and converted the fall in P-diast induced by i.v. tyramine into an increase. Thus the cardiovascular effects of exogenous noradrenaline are mainly characterized by alpha(1)-adrenoceptor-mediated vasoconstriction and the actions of endogenous noradrenaline (released by i.v. tyramine) by beta(1)-adrenoceptor-mediated positive inotropic effects. The rise in P-syst with i.v. tyramine most likely reflects positive inotropism and not a vascular 'pressor' response.