Peripheral sympatholytic actions of four AT1 antagonists: Are they relevant for long-term antihypertensive efficacy?

Andreas Dendorfer*, Peter Dominiak, Klaus Tempel, Walter Raasch

*Korrespondierende/r Autor/-in für diese Arbeit
9 Zitate (Scopus)


Background: Angiotensin II causes hypertension not only by direct constriction of vascular smooth muscle, but also by facilitating the release of noradrenaline from sympathetic terminals and by enhancing vascular noradrenaline sensitivity. AT1 receptor antagonists attenuate all these actions, but display some evidence of substance-related selectivities. Objective: The contribution of pre- or postsynaptic impairment of sympathetic transmission to long-term antihypertensive efficacy should be determined for four structurally different, clinically approved AT1 antagonists. Design: Spontaneously hypertensive rats were treated with candesartan, eprosartan, irbesartan, or losartan via osmotic minipumps for 4 weeks at doses yielding identical reductions of blood pressure. Maximum efficacy was obtained with a tripled dose of candesartan. Methods: In the pithed rat model, stimulus/response dependencies were determined for vasopressor effectivity of preganglionic electrical stimulation, and of intravenous bolus applications of noradrenaline and angiotensin II. Results: Losartan, irbesartan, eprosartan, and candesartan at doses of 5, 40, 20, and 0.05 mg/kg per day, were equally effective in reducing basal systolic blood pressure (-42 mmHg), and the vasopressor potency of angiotensin II (approximately 10-fold). The efficacies of preganglionic stimulation and exogenous noradrenaline were unaltered, with the exception of irbesartan, which reduced vascular noradrenaline sensitivity. The tripled dose of candesartan further reduced basal and angiotensin II-stimulated blood pressures, and significantly attenuated vascular noradrenaline sensitivity. Conclusion: AT1 antagonists at doses that effectively reduce blood pressure in chronic therapy do not generally suppress peripheral sympathetic function. A potential interaction consists in a reduction of vascular noradrenaline sensitivity, which can be considered as a class effect of AT 1 antagonists at high dosage.

ZeitschriftJournal of Hypertension
Seiten (von - bis)1861-1867
PublikationsstatusVeröffentlicht - 01.01.2005

Strategische Forschungsbereiche und Zentren

  • Forschungsschwerpunkt: Gehirn, Hormone, Verhalten - Center for Brain, Behavior and Metabolism (CBBM)


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