Proceedings of The Physiological Society

University College Cork (2004) J Physiol 560P, C5

Communications

BRAIN ANGIOTENSIN II (AII) AND THE BAROREFLEX CONTROL OF RENAL SYMPATHETIC NERVE ACTIVITY (RSNA) IN THE CONSCIOUS RAT

Huang,Chunlong ; Johns,Edward J;

1. Department of Physiology, University College Cork, Cork, Ireland.


The aim of the present study was to determine whether the role of brain AII in mediating/modulating the baroreflex control of RSNA was present in the conscious state. The angiotensin AT1 receptors within brain were manipulated by feeding a high Na diet in the post-weaning period, and by intracerebroventricular (icv) administration of antisense oligodeoxy-nucleotides (ASODN) directed against the AT1 receptor gene. Male Wistar rats (4 weeks old) were fed a regular (0.25%) or a high (3.1%) Na diet for 7 weeks. The rats were anaesthetised with pentobarbital sodium (60 mg/kg ip). The left carotid artery and right jugular vein were cannulated for monitoring blood pressure (BP) and heart rate (HR), and giving drugs. The left kidney was exposed and electrodes sealed onto the renal nerve. Using a sterotaxic frame, a guide cannula was implanted into the right lateral cerebroventricle. The animals recovered for 3 days before entering the study. BP, RSNA and HR were measured during iv phenylephrine hydrochloride and sodium nitroprusside (both at 10μg) before, 1 and 2 days after the icv infusion of the ASODN (5′TAACTGTGGCTGCAA) for the promoter region of the AT1 receptor gene, at 50μg. Animals were killed with an anaesthetic overdose. Baroreflex curves for both RSNA and HR were constructed (Miki et al, 2003). Data (means±SEM) were subjected to Student's t test and significance taken as P<0.05. In rats fed the regular diet (n=5), BP was 112±3 mmHg, HR was 479±14 beats min-1 (bpm) and RSNA 0.33±0.10 mVs-1. Logistic model parameters describing the baroreflex curves for RSNA, i.e. A1 (range), A2 (slope), A3 (mid-point BP) and A4 (minimum RSNA or HR), were 185.5±13.4%, 0.080±0.01% mmHg-1, 105.4±4.3 mmHg, and 11.0±8.3%, respectively and those for HR were 222±31 bpm, 0.082±0.012 bpm mmHg-1, 120.4±2.7 mmHg and 305±21 bpm, respectively. They were unchanged on days 1 and 2 following the icv ASODN. In rats fed a high Na diet (n=5), basal values of BP, HR, RSNA and baroreflex curve parameters were comparable to those in the rats on a normal sodium intake. However, A2 for RSNA, the sensitivity of the baroreflex curve, increased by 39.7% (P<0.05) 1 day after the icv ASODN, but returned to basal levels by day 2. These data showed that the ASODN to the angiotensin AT1 receptor gene caused a long acting increase in baroreflex sensitivity for RSNA. This would suggest that the involvement of endogenous AII within the brain in mediating/modulating the baroreflex control of RSNA in the conscious rat became more important after feeding a high Na diet in the post-weaning period.

Where applicable, experiments conform with Society ethical requirements