Proceedings of The Physiological Society

University College Dublin (2009) Proc Physiol Soc 15, C51

Oral Communications

Similar cardiovascular autonomic changes during the development of renovascular and angiotensin II (ANGII) induced hypertension in rats

M. A. Toward1, E. B. Oliveira-Sales1,2, R. R. Campos2, S. Kasparov1, J. F. Paton1

1. Physiology and Pharmacology, Bristol Heart Institute, University of Bristol, Bristol, United Kingdom. 2. Fisiologia Cardiovascular UNIFESP, Escola Paulista de Medicina Rua Botucatu, Sao Paulo, Brazil.


Hypertension remains a serious clinical problem. Numerous rodent models of hypertension have been developed to allow studies into possible causative mechanisms. Two such models are the chronic ANGII infusion and renovascular hypoperfusion (two kidney one clip; 2K1C). Although both models depend on activation of ANGII type 1 receptors, it is not known when and if the autonomic nervous system is engaged in the development and/or maintenance of the resultant hypertension. The development of hypertension in both models was documented using 24 hour radio-telemetry recording of arterial pressure (AP) and heart rate (HR) in conscious freely moving rats. Hey Presto software (Waki et al, 2006) was used to calculate spontaneous baroreflex gain (sBRG) and indices of autonomic function from the AP and HR variabilities by spectral analysis. ANGII model: Rats (male, 250-350g, n=12) were anaesthetised with a mixture of ketamine (60mg kg-1) and medetomidine (250μg kg-1, both i.m.) and radio-transmitters installed. Continuous recordings of AP and HR were made for 3 days prior to, and 10 days during, osmotic minipump driven infusion of ANGII (800ng/kg/min, s.c.). 2K1C model: Rats (male, 150-180g) were anaesthetised as above and radio-transmitters installed plus the left renal artery was partially obstructed with a silver clip of 0.2 mm width (n=6) or sham surgery (n=6). Recordings of AP and HR were made for 6 weeks. Values are means ± S.E.M., compared by ANOVA. Both models exhibited similar alterations in autonomic indices especially when the hypertension plateaued. For both the 2K1C and the ANGII group AP rose to similar levels (e.g. 185±15 mmHg vs. 103±10 for sham rats and 150±3 vs. 91±3 mmHg pre-infusion, p<0.05 respectively). Additionally, HR was elevated (ANGII: 409±10 vs. 368±5 bpm pre-infusion, p<0.05; 2K1C: 468±11 vs. 382±11 sham treated, p<0.05), very low frequency of systolic blood pressure increased (ANGII: 6.8±0.5 vs. 5.4±0.2 mmHg2 pre-infusion, p<0.05; 2K1C: 7.0±0.3 vs. 3.9±0.3 mmHg2 sham treated, p<0.05), high frequency of the pulse interval was reduced (ANGII: 10.6±1.5 vs. 15.0±1.1 ms2 pre-infusion, p<0.05; 2K1C: 9.6±0.5 vs. 16.7±0.9 ms2 sham, p<0.05) and sBRG was reduced (ANGII: -1.1±0.3 vs. -2.0±0.1 bpm/mmHg pre-infusion, p<0.05; 2K1C: -0.83±0.05 vs. -2.5±0.17 bpm/mmHg , sham, p<0.05). Thus, these established models of experimental hypertension are associated with failure of the parasympathetic component of the baroreflex and increased sympathetic vasomotor activity. These data suggest that chronically increased peripheral levels of ANGII, resulting from exogenous infusion or renal hypoperfusion, may cause hypertension via mechanisms involving central modulation of both cardiovascular autonomic activity and baroreflex function.

Where applicable, experiments conform with Society ethical requirements