Abstract This study investigated the role of brain AT1 and AT2 receptors and the nitric oxide (NO) system in modulating renal sympathetic nerve activity (RSNA) baroreflex in unanaesthetised rats. Baroreflex gain curves (BRC) were generated following intracerebroventricular (I.C.V.) infusion of saline, Ang II, or Ang II combined with either losartan, PD123319 (AT2 antagonist), or L-NAME (NO synthase inhibitor). An AT2 agonist (CGP42112) was also infused I.C.V. with L-NAME. RSNA baroreflex sensitivity increased by 60% ( P = 0.004) following losartan compared to saline (-4.8 ± 1.9 vs. -3.0 ± 0.9), but not after CGP42112. I.C.V. Ang II increased maximum gain by ~ 70% ( P = 0.003) compared to saline (-5.0 ± 1.6 vs. -3.0 ± 0.9). This effect was reversed when Ang II was co-infused with PD123319 (-3.7 ± 1.1), but not losartan. I.C.V. CGP42112 increased the overall response range of the baroreflex but lowered the minimum level it could reach compared to saline ( P = 0.03 − 0.02). The baroreflex effects of I.C.V. CGP42112 ( P = 0.013), but not Ang II, were abolished when co-infused with L-NAME. These findings demonstrate an important facilitatory role for AT2 in baroreflex regulation of RSNA in unanaesthetised rats at basal brain levels of Ang II, a mechanism that is dependent on a functional NO system. By contrast, AT1 exerts an inhibitory effect on the baroreflex that is independent of NO. These observations suggest that targeting central AT2 receptors may represent a potential therapeutic strategy for conditions such as neurogenic hypertension, where impaired baroreflex function is present.
Abdulla et al. (2025) studied this question.