gms | German Medical Science

27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Liga zur Bekämpfung des hohen Blutdrucks – Deutsche Hypertonie Gesellschaft e. V.

26. bis 29.11.2003, Bonn

AT1-receptor blockade lessens noradrenaline induced rise of blood pressure due to an improved noradrenaline uptake

Ein Noradrenalin-induzierter Blutdruckanstieg ist aufgrund einer gesteigerten Noradrenalin-Wiederaufnahme nach AT1-Blockade vermindert

Meeting Abstract (Hypertonie 2003)

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  • presenting/speaker W. Raasch - Universitätsklinikum Schleswig-Holstein (Lübeck, D)
  • A. Dendorfer - Universitätsklinikum Schleswig-Holstein (Lübeck, D)
  • P. Dominiak - Universitätsklinikum Schleswig-Holstein (Lübeck, D)

Hypertonie 2003. 27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Bonn, 26.-29.11.2003. Düsseldorf, Köln: German Medical Science; 2004. Doc03hochV39

The electronic version of this article is the complete one and can be found online at:

Published: November 11, 2004

© 2004 Raasch et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Blockade of AT1-receptors reduce the blood pressure response to noradrenaline (NA)-induced increase in blood pressure in isolated vessels and in-situ preparations. The underlying mechanisms should be clarified.

Diastolic blood pressure (DBP) was recorded to sequentially increasing doses of NA (10-12-10-7mol/kg) in pithed rats treated with tubocurarine, propranolol and atropine.

Pretreatment with candesartan (CAND 10-1000µg/kg, i.v.) increased ED50 of NA to a maximum of 20-fold compared to controls (1.3nmol/kg), while leaving the maximal rise in DBP unaffected. CAND inhibited the DBP response to NA (1nmol/kg) with an ID50 of 52.5µg/kg but did not alter the reactivity to vasopressin (130ng/kg). The AT1-specificity was confirmed with losartan (LOS, 30 mg/kg), since ED50 was also 15-fold enhanced. Inhibition of uptake-1 or alpha2-autoreceptors with desipramine (DES 0.5mg/kg) or rauwolscine (RAU 3mg/kg) diminished the differences in ED50 values of NA between LOS- and control-rats by 63% and 21%, respectively, compared to DES- and RAU-free rats. Under a combined blockade of uptake-1 and alpha2-autoreceptors, ED50 values of NA were identical in LOS and control groups. Depletion of endogenous catecholamines in reserpine (RES 5 mg/kg) pretreated rats increased DBP response to NA (+33%). Under RES-pretreatment, LOS, DES or a combination thereof failed to alter the NA-induced increase in DBP.

Our experiments show that the reduced vascular NA-reactivity after AT1-blockade is dependent on an intact sympathetic innervation and can be ascribed to an enhancement of NA uptake-1 and of an alpha2-mediated suppression of NA secretion. The new mechanism may contribute to the antihypertensive efficacy of AT1-blockers.