Increasing evidence supports a role for brain angiotensin II in influencing autonomic outflow following sensory input from the somatic and cardiovascular systems. Indeed, recent studies (Phillips et al. 1994) have shown significant decreases in basal levels of blood pressure (BP) in the spontaneously hypertensive rat (SHR) following administration of antisense oligodeoxy-nucleotides (ASODN) directed against the angiotensin AT1-receptor. What these studies did not address was how the autonomic outflow was modulated. The aim of this study was to examine how the pattern of activity contained within the renal nerve signal of the stroke-prone spontaneously hypertensive rat (SHR-SP) was altered following treatment with ASODN targeted at the AT1-receptor gene.
Two groups of male SHR-SP were given 50 µg of either sense (SODN) or ASODN, an inhibitor of AT1-receptor gene transcription, into the right lateral cerebroventricle (I.C.V.) under isoflurane anaesthesia. One day later the rats were anaesthetised using I.V. α-chloralose/urethane (12/180 mg ml-1), 0.7-0.9 ml. BP was measured from the femoral artery and saline (150 mM NaCl) was infused into the femoral vein at 3 ml h-1. The left kidney was exposed and the renal nerves were placed on bipolar electrode wires. Basal BP, heart rate (HR) and RSNA were recorded over 3.5 min and during the last minute data were collected at 1 kHz to generate a power spectrum from 0 to 10 Hz. Activation of the sympathetic nervous system was achieved by two 0.15 ml S.C. injections of capsaicin (1 mg ml-1) over 3.5 min. The ODNs used have been reported (Phillips et al. 1994). The rats were killed using an overdose of anaesthetic. Experiments accorded with UK legislation. Data (means ± S.E.M.) were analysed using a Student’s t test with significance taken at P < 0.05.
BP and HR were reduced in those animals given ASODN (n = 6) compared with those given the control SODN (n = 7) (108 ± 1 vs. 141 ± 3 mmHg, P < 0.0001; 3.6 ± 0.3 vs. 5.3 ± 0.2 Hz, P < 0.001, respectively), although integrated RSNA was not different. The power spectral parameters showed that basal levels of percentage and absolute power of the RSNA at the HR frequency were significantly lower in the animals given ASODN (8.1 ± 2.5 vs. 37.0 ± 3.1 %, P < 0.0001; 0.34 ± 0.10 vs. 1.96 ± 0.56 W, P < 0.05, respectively), but total power was not different between groups. Following the somatosensory challenge, the absolute change in BP and HR were all reduced in the rats given ASODN (P < 0.001 and P < 0.01, respectively). The increases in both percentage power and absolute power at the HR frequency were smaller following capsaicin treatment (P < 0.05) but the total power of the RSNA was not significantly different between groups.
These findings suggested that central angiotensin II may be involved in mediating both basal and reflex control of autonomic outflow. They also support the view that central angiotensin II can modulate the pattern of activity contained within the renal nerve signal of the SHR-SP. These findings are supported by previous data from our group (Dent & Johns, 2000), using SHR-SP, and from the work of others using SHR, given I.C.V. ASODN targeted against the angiotensinogen gene.