ISSN:
1432-1912
Keywords:
Antidepressant drugs
;
(+)-Oxaprotiline
;
Prazosin
;
Uptake
;
α1-Adrenoceptors
;
Noradrenaline release
;
Adrenaline release
;
Sympathetic outflow
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary Inhibition of uptake, in the central nervous system leads to a decrease of sympathetic outflow to many tissues; central a2-adrenoceptors are involved in this decrease. The aim of the present study was to compare the effects of the selective uptake, inhibitor (+)-oxaprotiline on the plasma kinetics of noradrenaline and adrenaline in anaesthetized and in conscious rabbits. [3H]Noradrenaline and [3H]adrenaline were infused iv. The arterial plasma concentrations of endogenous and radiolabelled noradrenaline and adrenaline were measured, and the clearance from and spillover into the plasma of noradrenaline and adrenaline were calculated. Results obtained in conscious and anaesthetized rabbits were similar. (+)-Oxaprotiline 0.2, 0.6 and 1.8 mg kg−1 iv. dose-dependently reduced the clearance of [3H]noradrenaline from the plasma. The clearance of [3H]adrenaline was reduced less. The spillover of endogenous noradrenaline was decreased by up to 35%. In contrast, the spillover of adrenaline tended to be enhanced. Prazosin 0.1 and 1 mg kg−1 was injected iv. in a second part of each experiment. It lowered the blood pressure and caused a marked increase in noradrenaline spillover but no increase or even a decrease in adrenaline spillover. The results are compatible with the following hypothesis. The sympathetic outflow from the central nervous system is subject to a twofold a-adrenoceptor-mediated modulation: α-adrenoceptor-mediated inhibition and α1-adrenoceptor-mediated excitation. In the control of the sympathetic outflow to many extra-adrenal tissues, the α2-adrenergic inhibition prevails. Uptake1 inhibitors depress sympathetic outflow to such tissues by enhancing the α2-adrenergic inhibition. In the regulation of the sympathetic outflow to the adrenal medulla, in contrast, α2-adrenergic inhibition and α1-adrenergic excitation have a similar impact. Uptake, inhibitors, hence, cause little change in adrenaline release: the two opposing influences cancel out. Prazosin produces an increase in noradrenaline but not adrenaline release because the loss of the central α1 sympathoexcitation attenuates at best slightly the baroreflex to most extra-adrenal tissues but dampens markedly the baroreflex to the adrenal medulla.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00169152
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