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Role of angiotensin AT1 receptor in the cardiovascular response to footshock

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Abstract

This study assessed the effect of non-peptide angiotensin II receptor subtype antagonists on the cardiovascular response to footshock. Effects of electric stimulation (1, 2 or 5 Hz) on mean arterial pressure (MAP) and heart (HR) were determined. Peripheral or central administration of losartan, an angiotension AT1 receptor antagonist (1 or 10 mg/kg s.c., or 10, 30 or 100 ωg/5 ωl i.c.v.), inhibited the mean arterial pressure response but not the heart rate response to footshock. In contrast, the MAP response to exogenous administration of norepinerphrine was not inhibited by subcutaneous administration of losartan (10 mg/kg). Given at 100 ωg/5 ωl i.c.v., the angiotensin AT2-selective receptor antagonist, PD 123319, did not reduce hemodynamic responses to electric stimulation. These results suggest that, in acute stress, endogenous angiotensin II facilitation of noraddrenergic transmission is mediated through the angiotensin AT1 receptor.

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    Citation Excerpt :

    We also intended to investigate the impact of chronic footshock stress on activation of the sympathoadrenal system, as chronic activation of this system can lead to increased catecholamine release from the sympathetic nerve terminals and adrenal gland and therefore may contribute to a number of cardiovascular disorders in humans and experimental animals including hypertension (Grassi et al., 2008; Grassi et al., 2010; Lee et al., 1991; Parati and Esler, 2012). Specifically, we assessed the expression and phosphorylation of tyrosine hydroxylase (TH) and the levels of Ang II receptor type 1 (AT1R) in the adrenal gland and in the stellate ganglia — the indices previously associated with chronic stress and/or sympathetic activation (Baruchin et al., 1990; Cierco and Israel, 1994; Dendorfer et al., 2002; Fluharty et al., 1983; Kvetnansky et al., 2004; Ma et al., 2001; Nankova et al., 1996; Powis and Obrien, 1991; Stromberg et al., 1991). All animal procedures were approved by the Ethics Committee of the University of Newcastle (Australia) and animals were cared for according to the principles of the Australian code of practice for the care and use of animals for scientific purposes (7th edition 2004).

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