Abstract 1592: The Role of Central AT2R in Regulation of Sympathetic Outflow of CHF Rabbits
In a previous study we showed that elevated central angiotensin II (AngII) plays a critical role in the sympatho-excitation in chronic heart failure (CHF) via stimulation of angiotensin type 1 receptors (AT1R) in the rostral ventrolateral medulla (RVLM). However, it has been well documented that the brain expresses both AT1R and AT2R. Although the AT1R is dominant in the adult organism, an increase of AT2R expression has been observed under some pathological conditions, including CHF. The purpose of the current experiment is to determine the role of the AT2R in the regulation of sympathetic activity in CHF. Experiments were carried out on 25 male New Zealand White rabbits that were divided into a sham and a CHF group. All rabbits were identically instrumented to record renal sympathetic nerve activity (RSNA) responses to intracerebroventricular (icv) injection of the AT2R agonist CGP-42112 alone or in combination with the AT1R antagonist losartan or/and AT2R antagonist PD123319. Experiments were carried out in the conscious state. Western blot were used to measure protein expression of AT1R and AT2R in the RVLM. The table⇓ shows the AT1R and AT2R expression and the RSNA responses. CGP-42112 by itself evoked a small reduction in RSNA however, after blockade of AT1R (losartan), stimulation of AT2 receptors with CGP-42112 evoked a significant decrease in RSNA in CHF. On the other hand, RSNA increased after central blockade of AT2R with PD123319 in CHF rabbits. These results indicate that both AT1R and AT2R expression of RVLM are up regulated in CHF rabbits, and stimulation of AT2R significantly decreases the RSNA in CHF rabbits. CGP, CGP-42112; Los, Losartan; PD, PD123319. *P < 0.05 compared with sham; †P < 0.05 compared with control; ‡P < 0.05 compared with CGP 0.1 μg.