Reduction of vascular noradrenaline sensitivity by AT1 antagonists depends on functional sympathetic innervation

Walter Raasch*, Peter Dominiak, Andreas Ziegler, Andreas Dendorfer

*Corresponding author for this work
17 Citations (Scopus)


Blockade of angiotensin II type-1 (AT1) receptors has been shown to reduce the magnitude of the blood pressure response to noradrenaline in pithed rats via an unidentified mechanism. Dose-response curves were established for the noradrenaline-induced (10-12 to 10-7 mol/kg) increase of diastolic blood pressure in pithed rats treated with tubocurarine, propranolol, and atropine. Candesartan (1 mg/kg) increased the ED50 of the noradrenaline response (1.3±0.1 nmol/kg) up to 20-fold. Vasopressor responsiveness to noradrenaline was attenuated specifically, whereas the vasopressin-induced increase in diastolic blood pressure was maintained. Specific involvement of AT1 receptors was confirmed by equivalent actions of losartan. Blockade of norepinephrine transporter or α2-adrenoceptors using desipramine or rauwolscine reduced the losartan-induced shifts in the ED50 values of noradrenaline by 63% and 21%, respectively. Combined blockade of norepinephrine transporter and α2-adrenoceptors eliminated the influence of losartan on noradrenaline sensitivity (ED50 5.5±1.3 versus 5.6±1.2 nmol/kg), a result also observed after sympathetic denervation by reserpine (ED50 7.1±0.8 versus 7.8±0.8 nmol/kg). Our experiments show that the reduction of vascular noradrenaline sensitivity by AT1 blockade is dependent on the intact functioning of both neuronal noradrenaline uptake via norepinephrine transporter and presynaptic α2- mediated autoinhibition, exclusively provided by the sympathetic innervation. These newly identified mechanisms may contribute to the antihypertensive and protective actions of AT1 blockers.

Original languageEnglish
Issue number3
Pages (from-to)346-351
Number of pages6
Publication statusPublished - 01.09.2004

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


Dive into the research topics of 'Reduction of vascular noradrenaline sensitivity by AT1 antagonists depends on functional sympathetic innervation'. Together they form a unique fingerprint.

Cite this