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Blockade of angiotensin AT1-receptors in the rostral ventrolateral medulla of spontaneously hypertensive rats reduces blood pressure and sympathetic nerve discharge

The Howard Florey Institute of Experimental Physiology and Medicine, The University of Melbourne, Vic., 3010, Australia, a.allen{at}hfi.unimelb.edu.au

Microinjections of angiotensin II (Ang II) into the rostral ventrolateral medulla (RVLM) induce a sympathetically-mediated increase in blood pressure (BP), through an interaction with AT₁-receptors. Under basal conditions in anaesthetised animals, microinjections of AT ₁-receptor antagonists into the RVLM have little, or no effect on BP, suggesting that the angiotensin input to this nucleus is not tonically active. In contrast, microinjections of AT₁-receptor antagonists into the RVLM of sodium-deplete rats and TGR(mRen2)27 rats, induce a depressor response through sympatho-inhibition. This indicates that when the renin-angiotensin system is activated, angiotensin can act in the RVLM to support sympathetic nerve discharge and BP. This study examined whether angiotensin inputs to the RVLM are activated in the spontaneously hypertensive rat — a pathophysiological model which displays increases in both brain angiotensin levels and sympathetic nerve activity. Bilateral microinjections of the AT ₁-receptor antagonist candesartan cilexetil, (1 nmol in 100 nl), into the RVLM of the spontaneously hypertensive rat induced a significant decrease in lumbar sympathetic nerve discharge (-18±2%) and BP (140±6 to 115±6 mmHg). In contrast, similar microinjections in the Wistar-Kyoto (WKY) rat had no effect on BP or sympathetic nerve discharge. These results are interpreted to suggest that Ang II inputs to the RVLM are activated in the spontaneously hypertensive rat to maintain an elevated level of sympathetic nerve discharge, even in the face of increased BP.

Key Words: hypertension • SHR • RVLM • renin-angiotensin system

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Journal of Renin-Angiotensin-Aldosterone System, Vol. 2, No. 1 suppl, S120-S124 (2001)
DOI: 10.1177/14703203010020012101


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