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.Methods:
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 Nω-nitro-L-arginine methyl ester (L-NAME) (nitric oxide synthase inhibitor).Results:
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%).Conclusion:
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.