This study investigated the hypothesis that angiotensin II (type 2) (AT2) receptor activation to modulate the renal sympatho-inhibition to saline volume expansion was dependent on nitric oxide production.
Renal sympatho-inhibition to a saline volume expansion (VEP, 0.25% body weight/min i.v. for 30 min) was studied following intracerebroventricular (ICV) saline, CGP42112 (CGP, AT2 agonist), PD123319 (AT2 antagonist), and losartan (AT1 antagonist), and then in combination with N-nitro-L-arginine methyl ester (L-NAME) (nitric oxide synthase inhibitor).
ICV saline, PD123319, CGP, and losartan did not change baseline mean arterial pressure, heart rate, or renal sympathetic nerve activity (RSNA). VEP decreased RSNA in all groups by 58-62% (P<0.05). CGP enhanced the decrease in RSNA compared to saline (74 vs. 60%; P<0.05), whereas PD123319 was without effect (58 vs. 57%). L-NAME only increased baseline RSNA when co-administered with PD123319 (P<0.05). VEP-induced reduction in RSNA following L-NAME was less than during ICV saline (46 vs. 62%; P<0.05). In the group where PD123319 preceded L-NAME, the fall in RSNA was smaller than when PD123319 was infused alone (40 vs. 63%; P<0.05), but not if PD123319 followed L-NAME (52 vs. 44%). L-NAME did not change the magnitude of VEP-induced sympatho-inhibition following CGP (67 vs. 60%). Losartan enhanced the renal sympatho-inhibition to VEP (70 vs. 62%; P<0.05), the magnitude of which was unchanged when L-NAME was present (70 vs. 65%).
AT2 receptor activation enhances the VEP-induced reduction in RSNA. Although nitric oxide is important in allowing the normal renal sympatho-inhibitory response to VEP, this is not dependent on AT2 receptors.