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  • 1
    ISSN: 1432-1912
    Keywords: Key words Noradrenaline (i.v.) ; Tyramine (i.v.) ; Adrenoceptors ; Muscarinic receptors ; Systolic time intervals
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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 μg/kg/min. Noradrenaline and tyramine were administered in the absence and presence of α1-adrenoceptor blockade with doxazosin (2 mg p.o.), α2-adrenoceptor blockade with yohimbine (15 mg p.o.), selective β1-adrenoceptor blockade with bisoprolol (15 mg p.o.) and muscarinic receptor blockade with atropine (15 μg/kg i.v. loading dose followed by 0.15 μg/kg/min by i.v. infusion). Vasoconstrictor effects were assessed by measurement of diastolic blood pressure (Pdiast) and myocardial effects by measurement of systolic time intervals, namely the duration of electromechanical systole corrected for heart rate (QS2c). I.v. noradrenaline increased Pdiast (Δmax 17 mmHg) and this was nearly completely suppressed by doxazosin but only slightly blunted by yohimbine. Noradrenaline also slightly shortened QS2c (Δmax –22 ms), and this was potentiated by both doxazosin and yohimbine and completely blocked by bisoprolol. I.v. tyramine reduced Pdiast (Δmax –7 mmHg), which was not affected by α1-adrenoceptor blockade, and profoundly shortened QS2c (Δmax -104 ms) which was significantly correlated with a marked increase in systolic blood pressure (Psyst) (Δmax 57 mmHg). The shortening of QS2c and the rise in Psyst were not influenced by α-adrenoceptor blockade but were antagonized by bisoprolol. Atropine potentiated the blood pressure rise and the shortening of QS2c induced by i.v. noradrenaline and converted the fall in Pdiast induced by i.v. tyramine into an increase. Thus the cardiovascular effects of exogenous noradrenaline are mainly characterized by α1-adrenoceptor-mediated vasoconstriction and the actions of endogenous noradrenaline (released by i.v. tyramine) by β1-adrenoceptor-mediated positive inotropic effects. The rise in Psyst with i.v. tyramine most likely reflects positive inotropism and not a vascular ‘pressor’ response.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1912
    Keywords: Key words Noradrenaline (i.v.) ; Tyramine (i.v.) ; Adrenoceptors ; Muscarinic receptors ; Ageing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this study, carried out in six elder healthy volunteers (mean age: 61 years), was to determine the influence of muscarinic receptor blockade with atropine (15 µg/kg i.v. loading dose followed by 0.15 µg/kg/min by i.v. infusion) on the effects of i.v. infusions of noradrenaline (5 incremental doses of 10-120 ng/kg/min) or tyramine, that releases endogenous noradrenaline (4 incremental doses of 5-20 µg/kg/min), on blood pressure, heart rate and systolic time intervals (STI’s, as a measure of positive inotropism). These results were compared with those recently published for young healthy volunteers (mean age: 26 years; Schäfers et al. 1997). Noradrenaline caused increases in systolic and diastolic blood pressure, decreases in heart rate and a shortening of STI’s that were not different from those in young volunteers. Atropine did not significantly affect these hemodynamic responses to noradrenaline, while in young volunteers it significantly enhanced noradrenaline-induced blood pressure increases and converted the heart rate decrease into an increase. In the present study in elder volunteers, tyramine caused a smaller increase in systolic blood pressure than in the previous study in young volunteers; in addition, it slightly increased diastolic blood pressure while it decreased diastolic blood pressure in young volunteers. Atropine did not significantly affect the hemodynamic effects of tyramine in the elder volunteers, while in the young volunteers it enhanced the increase in systolic blood pressure and converted the decreases in diastolic blood pressure and heart rate into increases. These results indicate a) that ageing is accompanied by a blunted baroreflex-mediated parasympathetic activation resulting in reduced cholinergic vasodilation and decreases in heart rate, and b) that ageing is associated with a decreased responsiveness of (cardiac) β-adrenoceptors and (vascular) α1-adrenoceptors which is only unmasked when the counterregulatory action of parasympathetic activation is removed.
    Type of Medium: Electronic Resource
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