Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, PC19
Chronic electrical stimulation of the ventral lateral periaqueductal grey (vlPAG) evokes a persistent and substantial hypotensive response in spontaneously hypertensive (SH) but not normotensive rats
F. McBryde1, N. Patel2, J. Paton1
1. School of Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom. 2. Department of Neurosurgery, Frenchay Hospital, Bristol, United Kingdom.
Deep brain stimulation of the vlPAG is used for the clinical treatment of chronic neuropathic pain in man. It also produces sustained reductions in arterial pressure (AP) in hypertensive patients (Patel et al. Neurology, 2011). We have developed an implantable electrical stimulation system and applied it to the vlPAG of conscious, freely moving rats. AP and heart rate (HR) responses were measured via telemetry to explore potential central mechanisms. Devices were implanted under ketamine and dormitor anesthesia (60mg.kg-1/250ug.kg-1 intraperitoneal injection). Quiescent rats were stimulated for 60 min at a series of frequencies (10-40 Hz) with >30 min recovery between steps. SH rats (mean baseline AP 139±10mmHg; n=4) showed sustained and frequency-dependent AP reductions (12±2 vs 27±4mmHg; 10 vs 30 Hz, peak response; p<0.05). In contrast, in Wistar rats (mean baseline AP 101±9mmHg; n=2) smaller depressor responses were evoked (3±2mmHg vs 6±2mmHg; 10 vs 30Hz, peak response) which tended to return towards baseline levels after 20-30mins stimulation. Corresponding decreases in the low frequency (LF) power of systolic blood pressure were observed (SH 8.8±2.3 vs 1.9±0.5mmHg2; Wistar 1.4±0.5 vs 1.1±0.4mmHg2; baseline vs 30Hz), indicating that sympathetic outflow may be reduced. In SH rats the depressor response was maintained throughout 7 days of continuous 20Hz vlPAG stimulation (135mmHg to 121mmHg; baseline vs day 6; n=3) and associated with a reduction in the low frequency power of systolic blood pressure (4.8±2 vs 1.4±0.2mmHg2; baseline vs day 6). In Wistar rats the reduction in blood pressure was smaller (99 vs 95mmHg) and no change in LF power observed (0.5 vs 0.4mmHg2). Thus, the vlPAG of the SH rat is a more effective depressor site than in Wistar rats, and this may be due to a more pronounced suppression of the sympathetic nervous system. Our current studies are now determining the mechanisms for this.
Where applicable, experiments conform with Society ethical requirements