Chronic angiotensin II infusion modulates angiotensin II type I receptor expression in the subfornical organ and the rostral ventrolateral medulla in hypertensive rats

Abstract

Blood-borne angiotensin II (Ang II) has profound effects on the central nervous system, including regulation of vasopressin secretion and modulation of sympathetic outflow. However, the mechanism by which circulating Ang II affects the central nervous system remains largely unknown. We tested the hypothesis that increased circulating levels of Ang II activate angiotensin type I (AT1) receptors in the subfornical organ (SFO), increasing the Ang II signalling in the rostral ventrolateral medulla (RVLM). Male Wistar rats were subcutaneously implanted with two 14-day osmotic minipumps filled with Ang II (150ng/kg/minute), Losartan (10mg/kg/day), or saline. In addition, AT1 receptor mRNA levels in the SFO and RVLM were detected by reverse transcription polymerase chain reaction (RT-PCR). Infusion of Ang II-induced hypertension (134 ± 10 mmHg vs 98 ± 9 mmHg, n = 9, p < 0.05), which was blunted by concomitant infusion of Losartan (105 ± 8 vs 134 ± 10 mmHg, n = 9, p < 0.05). In addition, hexamethonium produced a greater decrease in blood pressure in Ang II-infused rats. Real time PCR revealed that chronic Ang II infusion induced an increase in AT1 receptor mRNA levels in the RVLM and a decrease in the SFO. Taken together, using combined in vivo and molecular biology approaches, our data suggest that Ang II-induced hypertension is mediated by an increase in sympathetic nerve activity, which seems to involve up-regulation of AT1 receptors in the RVLM and down-regulation of AT1 receptors in the SFO.

Keywords

Blood pressure ganglionic blocker hypertension losartan sympathetic activity

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