Our recent clinical findings have revealed that deep brain stimulation of the ventrolateral periaqueductal gray (vlPAG) decreases arterial pressure in patients with drug- and device-resistant hypertension ((1) and unpublished). However, the mechanism(s) underlying this effect is(are) not fully understood. Studies in anaesthetised, normotensive animals suggest that acute activation of the vlPAG induces hypotension and sympatho-inhibition (2,3). Therefore, in this study, we sought to determine the blood pressure response to electrical stimulation of the vlPAG in a conscious rat model of essential hypertension, the spontaneously hypertensive rat (SHR). (SH rats (male, 250-350g, n = 16) were anaesthetised (ketamine 60mg/kg and medetomidine 250µg/kg) and implanted with radio-transmitters to measure blood pressure. Rats recovered over 7-10 days and were re-anaesthetised (sodium pentobarbital 50mg/kg) and using stereotaxic coordinates a bipolar electrode was placed chronically into the PAG at ventral and dorsal sites (verified histologically post hoc; 0.8-1.0mm lateral to midline, 7.2-7.6mm caudal to bregma and 5.4-6.4mm ventral to the dura). Electrical stimulation (2-6V, 20-40Hz, 0.2ms pulse width) of the PAG was applied while recording blood pressure. The electrode was cemented at the site of maximal depressor response (present in 8 of 16 rats) and the rats recovered for 6-8 days before chronic PAG stimulation in conscious animals. Values are mean ± SEM. Electrical stimulation at histologically confirmed sites within the vlPAG decreased arterial pressure (-19±4 mmHg, n= 8; P<0.05, student’s t test) when rats were anaesthetised with sodium pentobarbital but did not decrease arterial pressure or heart rate in conscious, freely-moving rats. In 2 SHRs that had depressor responses under anaesthesia displayed a pressor effect in the conscious state. The hypotensive action of the vlPAG under anaesthesia has been attributed to inhibition of sympathetic preganglionic neurons (4). We therefore used an in situ decerebrate preparation (5) of juvenile SHRs (5 weeks old) to investigate whether activation of vlPAG neurons produced sympatho-inhibition below the threshold at which a blood pressure response could be observed. No measureable sympathetic responses were evoked from the vlPAG using either electrical stimulation (100µA, 20Hz, 0.2ms) or excitatory amino acid microinjections (D,L-Homocysteic acid, 1mM, 60nL). In contrast, sympatho-excitatory responses were evoked by both stimuli in the dorsal PAG. We conclude that the vlPAG is not a reliable antihypertensive locus in the SHR in which to model human deep brain stimulation. Whether the dorsal PAG in the SHR has utility as a model system for understanding intractable postural hypotension remains to be seen.