Role of angiotensin AT2 receptors and nitric oxide in the cardiopulmonary baroreflex control of renal sympathetic nerve activity in rats

Abstract

Objectives: 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 N-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.

Fig. 1

Time course of the reflex renal sympatho-inhibition due to volume expansion in the control group. After starting i.v. saline volume expansion, the percentage change in RSNA from the baseline was taken at 5 min intervals through the 30-min volume expansion period and the 30-min recovery period. *, # P<0.05, compared with the baseline level for the first and second volume expansion respectively. RSNA, renal sympathetic nerve activity.

Fig. 2

The renal sympathetic nerve activity responses to two sequential acute saline volume expansions in i.c.v. saline infusion followed by either saline (A), PD (B), CGP (C), Losartan (D) and L-NAME (E). The baseline value of RSNA was taken as 100% and the maximum sympatho-inhibition due to volume expansion was the average value over the 25-30 min while the recovery of RSNA was taken 30 min after stopping the saline challenge. *P<0.05, compared with baseline. # P<0.05, compared with the 25-30 min value of the first volume expansion. VEP, volume expansion.

Fig. 3

The renal sympathetic nerve activity responses to two sequential acute saline volume expansions in PD/PD+L-NAME (A), L-NAME/L-NAME+PD (B), CGP/CGP+L-NAME (C) and Losartan/Losartan+L-NAME (D). The baseline value of RSNA was taken as 100% and the maximum sympatho-inhibition due to volume expansion achieved at 25-30 min following the start of the saline volume load while the recovery of RSNA was taken after 30 min of stopping the saline challenge. *P<0.05, compared with baseline. # P<0.05, compared with the first volume expansion. VEP, volume expansion.