In the spontaneously hypertensive rat (SHR) hypertension is associated with raised sympathetic outflow. Why sympathetic activity is raised is unclear but if blood flow to the brain is impeded, blood pressure increases (Cushing effect) and there is a parallel increase in sympathetic outflow (Knapp, 1965). Our hypothesis is that the brainstem is highly sensitive to a correlate of perfusion such that flow reduction drives a proportionate increase in sympathetic outflow and arterial pressure (Paton et al., 2009). We postulate that cerebrovascular conductance is reduced in the SHR compared to the normotensive Wistar Kyoto rat (WKR). Having measured BP by tail cuff we prepared vascular corrosion casts of age-matched WKR and SHR rats according to the method of Krucker et al. (2006). Animals were killed according to the UK Animals (Scientific Procedures) Act 1986. On cessation of the circulation, a cannula was placed in the left ventricle and vascular constriction inhibited by flushing with a zero calcium, high magnesium phosphate buffer containing 100 µM hydralazine. After perfusion fixation (formaldehyde, 4%), the vasculature was filled with a urethane-based resin (Pu4ii, VasQtec). Perfusion pressure during flushing, fixation and resin infiltration was the systolic pressure previously recorded from each animal. Resultant casts were liberated by maceration using sodium hydroxide (10%) and hydrochloric acid (10 mM) at 55 oC. Casts were freeze-dried, sputter coated with gold and examined in a scanning electron microscope (SEM; FEI, Quanta 400). Our preliminary results relate to n=1 for each strain. Measurements of arterial diameter were made using software tools intrinsic to the SEM. Mann-Whitney U tests were used to make statistical comparisons of median values. Median values for basilar and vertebral artery diameter were smaller in the SHR compared to the WKR. Similarly, the diameters of branches arising from these arteries tended to be smaller in the SHR compared to the WKR. It should be noted that in the SHR, the diameter of the right vertebral (rv) artery (174 µm) was very much smaller than that of the left vertebral (lv) artery (272 µm), whereas, in the WKR, the diameters of the two arteries were similar (271 vs 291 µm). The fourth power of the vessel radius relative to the principle feeding artery (basilar, rv or lv) was calculated as an index of conductance and comparisons made within and between animals. This revealed that vascular conductance is substantially lower in the SHR than the WKR (P<0.05). Our preliminary findings are consistent with the hypothesis that the brainstem of the SHR has a lower vascular conductance than the WKR. Our findings resonate with a study of human tissue at post-mortem in which a reduction in calibre of the rv artery was strongly and inversely correlated with ante-mortem blood pressure (Dickinson, 1960).