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Differentiation in the Angiotensin II Receptor 1 blocker class on autonomic function

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Abstract

Autonomic function is disordered in cardiovascular disease states such as chronic heart failure (CHF) and hypertension. Interactions between the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS) may potentially occur at a number of sites. These include central sites (eg, rostral ventrolateral medulla), at the level of baroreflex control, and at the sympathetic prejunctional angiotensin II receptor 1 (AT1) receptor, which is facilitatory for norepinephrine release from the sympathetic nerve terminal. Therefore, drugs that block the RAAS may be expected to improve autonomic dysfunction in cardiovascular disease states. In order to test the hypothesis that RAAS inhibition directly reduces SNS activity, a pithed rat model of sympathetic stimulation has been established. In this model, an increase in frequency of stimulation results in a pressor response that is sympathetically mediated and highly reproducible. This pressor response is enhanced in the presence of angiotensin II and is reduced in the presence of nonselective AIIRAs that block both AT1 and AT2 receptor subtypes (eg, saralasin). AT1-selective antagonists have also been studied in this model, at pharmacologically relevant doses. In one such study, only the AT1 blocker eprosartan reduced sympathetically stimulated increases in blood pressure, whereas comparable doses of losartan, valsartan, and irbesartan did not. The reason(s) for the differences between eprosartan and other agents of this class on sympathetic modulation are not clear, but may relate to the chemical structure of the drug (a non-biphenyl tetrazole structure that is chemically distinct from the structure of other AIIRAs), receptor binding characteristics (competitive), or unique effects on presynaptic AT1 receptors.

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  1. Clinical Pharmacology Unit, Department of Epidemiology and Preventive Medicine/Department of Medicine, Monash University/Alfred Hospital, Commercial Road, 3181, Prahran, Victoria, Australia

    Henry Krum MBBS, PhD, FRACP

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  1. Henry Krum MBBS, PhD, FRACP
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Krum, H. Differentiation in the Angiotensin II Receptor 1 blocker class on autonomic function. Current Science Inc 3, S17–S23 (2001). https://doi.org/10.1007/s11906-001-0067-x

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