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Postsynaptic α 1 ‐ and α 2 ‐adrenoceptors in human blood vessels: interactions with exogenous and endogenous catecholamines

1987; Wiley; Volume: 17; Issue: 2 Linguagem: Inglês

10.1111/j.1365-2362.1987.tb02397.x

1365-2362

K Jie, P. van Brummelen, P. Vermey, Pieter B.M.W.M. Timmermans, P. A. van Zwieten,

EEG and Brain-Computer Interfaces

Abstract. The relative efficacy of epinephrine and norepinephrine on vascular α 1 ‐ and (α 2 ‐adrenoceptors and also the difference in vasoconstriction induced by exogenous norepinephrine as opposed to neuronally released norepinephrine were studied in the forearm of healthy volunteers. Intra‐arterial cumulative dose infusions of epinephrine and norepinephrine (0·6, 1·6 and 4·0 ng kg −1 min −1 ) were given in the presence of saline, the selective α 1 ‐antagonist doxazosin (0·1 μg kg min −1 ) the selective α 2 ‐antagonist yohimbine (1·0 μg kg min −1 ) and the combination of both antagonists. β‐Adrenoceptor‐mediated effects were prevented by a concomitant i.a. infusion of propranolol (10 μg kg −1 min −1 ). Forearm blood flow (FBF) was measured before each infusion and at the end of each dose step. Neuronal norepinephrine was released by i.a. infusion of tyramine in three cumulative doses (0·25, 0·50 and 1·25 μg kg −1 min −1 ) and by lower body negative pressure (LBNP, − 40 mmHg for 5 min). Changes in FBF were measured without and with concomitant i.a. infusions of the aforementioned doses of doxazosin and yohimbine. In the LBNP experiment the opposite arm was used as a control. Forearm blood flow was measured by plethysmography. Epinephrine and norepinephrine induced an equal and dose‐dependent vasoconstriction, which was significantly inhibited by doxazosin as well as yohimbine and to a greater extent by the combination of the antagonists. No differences were found between epinephrine and norepinephrine in this respect. Intra‐arterial tyramine induced a dose‐dependent vasoconstriction, which was inhibited by both doxazosin and yohimbine. The tyramine‐induced vasoconstriction was more effectively blocked by doxazosin than by yohimbine whereas the reverse was found for the vasoconstriction induced by infusion of norepinephrine. Lower body negative pressure produced a similar vasoconstriction in both arms. This vasoconstriction was not influenced by yohimbine, but was significantly inhibited by doxazosin. It is concluded that vasoconstriction induced by exogenous epinephrine and norepinephrine is due to stimulation of both α 1 ‐ and α 2 ‐adrenoceptors and that neuronally released norepinephrine preferentially activates postsynaptic α 1 ‐adrenoceptors. Moreover, epinephrine and norepinephrine have similar relative efficacies on both α‐adrenoceptor subtypes. These data support the view that postsynaptic α 1 ‐adrenoceptors are predominantly located intrasynaptically whereas postsynaptic α 2 ‐adrenoceptors are predominantly located extrasynaptically. It can also be reasoned that norepinephrine rather than epinephrine is responsible for α 2 ‐adrenoceptor mediated basal vascular tone.