Using the spontaneously hypertensive rat (SHR) as an animal model of essential hypertension we are working on a hypothesis that the condition is due, in part, to increased sympathetic activity that occurs in response to brainstem hypoperfusion. There is good evidence of increased sympathetic tone in adult humans with essential hypertension and in the SHR even at a prehypertensive (<5 week) age (see 1). Brainstem hypoperfusion causes an acute rise in blood pressure in humans and other species (1,2,3) and in humans, chronic hypertension correlates more closely with narrowing of the vertebral arteries than any other vessel (4). There is also evidence of anaerobic metabolism in the SHR brainstem and increased vertebral and basilar arterial wall thickness at the prehypertensive age (5,1). However, the functional significance of the latter histological changes in large vessels to resistance and flow remain unclear and were functionally investigated in the present study. Using a novel in vitro perfusion preparation, vascular resistance within the basilar arterial tree was measured in male 4-5 week SHR (n=7) and Wistar (n=9) rats. Under deep halothane (5%) anaesthesia, rats were decapitated at the 1st cervical level and decorticated. The brainstem with cerebellum was removed in cold (4°C) artificial cerebrospinal fluid (ACSF) and pinned down in a perspex chamber, ventral side up. The basilar artery was cannulated at its caudal end with a double-lumen theta glass pipette and tied in place with a fine silk suture. The preparation was both superperfused with warm (32°C) ACSF bubbled with 95% O2, 5%CO2 and perfused through one lumen of the cannula with gas bubbled ACSF (32°C) plus 1.5% polyethylene glycol at an initial rate of 0.22ml/min. The basilar artery was then clamped at its rostral end and warmed for 10 minutes. Flow was increased incrementally every 10 minutes across 6 flow rates and pressure recorded via a transducer attached to the second, fluid-filled lumen of the theta glass cannula. Average pressures were significantly higher (p= <0.05, T-test) across all flow rates in the SHRs and at the highest flow rate (1.2 ml/min) were 173 ±8 vs 140 ±6 (average ± SEM) mmHg; p=0.002. These data indicate increased vascular resistance within the brainstem of the pre-hypertensive SHR, which is consistent with the reported narrowing of the basilar artery relative to age matched normotensive rats (4). Our results support the hypothesis of enhanced cerebral vascular resistance predisposing to hypoperfusion-triggered increases in sympathetic vasomotor tone. Given the relative restrictive nature of the brainstem vasculature to flow in the SHR, we are currently comparing differences in activation of the sympathetic nervous system following sequential occlusion of the vertebral and carotid arteries in SHR and normotensive rats.