Conference Publication Details
Mandatory Fields
Barseem, H; Johns EJ;
Physiological Society Meeting
Contribution of angiotensin AT2 receptors to the baroreflex control of renal sympathetic nerve activity in anaesthetised rats
2010
Validated
()
Optional Fields
Manchester
01-JUL-10
03-JUL-10
Angiotensin II generated in the brain exerts a tonic inhibitory influence on baroreflex regulation of sympathetic nerve activity. This action is exerted via angiotensin AT1 receptors but there is evidence that AT2 receptors may also be involved and buffer the AT1 mediated effects. This study aimed to investigate whether brain AT2 receptors could modulate the sensitivity of the high pressure baroreflex regulation of renal sympathetic nerve activity (RSNA). Wistar rats (250-300g) were anaesthetised with 1ml chloralose/urethane (16.5/250mg/ml) I.P. Cannulae were inserted in the right femoral artery, for blood pressure (BP) measurement, and vein for saline infusion and supplementary anaesthetic given as 0.05ml every 30 min. A cannula was placed in the right intracerebroventricle (ICV) as previously described (Huang, 2005). The left kidney was exposed, a renal sympathetic nerve identified and then sealed onto recording electrodes. Baroreflex gain curves were produced for RSNA using a four parameter algorithm (Huang et al 2005) by raising and lowering BP using iv infusions of 0.2ml phenylephrine (50g/ml) or sodium nitroprusside (50g/ml) infused for 40s at 18ml/h. Saline was infused ICV at 40l/h and the first baroreflex curve was generated, thereafter, the icv infusion was switched to either PD123319 (50g/kg/min), an AT2 receptor antagonist (n=6) or CGP 42112 (50g/kg/min), an AT2 agonist (n=6) after which a second baroreflex curve was undertaken. RSNA parameters were expressed as % values, with 0% being the minimum value obtained during the phenylephrine infusion and 100% as the basal value. The animals were killed at the end of the experiment. Data, means S.E.M were compared using Wilcoxon signed rank test and significance taken at P<0.05. Baseline BP, heart rate (HR) and RSNA were similar in all groups at 1004mmHg, 3247 bpm and 152 v/s, respectively. Baroreflex parameters for the first test averaged for all rats gave the range, A1, as 1128 μV/s, the sensitivity, A2 as 0.0790.018%/mmHg, A3, the mid-point BP as 802 mmHg and the lowest point of the curve, A4, as 183%. ICV infusion of AT2 antagonist PD123319 significantly decreased the RSNA baroreflex sensitivity A2, from 0.120.03 to 0.020.01%/mmHg (P<0.05) but had no effect on A1, A3 or A4. ICV infusion with the AT2 agonist significantly increased RSNA baroreflex sensitivity A2 from 0.360.15 to 0.790.02%/mmHg (P<0.05) but had no effect on either A1, A3 or A4. These results demonstrate that activation of angiotensin AT2 receptors depresses the sensitivity of the baroreflex regulation of RSNA. They suggest that activation of the AT2 receptors partially offsets the inhibitory action of angiotensin acting via AT1 receptors.
Grant Details