Backgrounds and Purpose: Cerebral microvascular disease (CMD) is increased in the presence of aortic stiffening. We have reported a close relation between carotid flow augmentation index (FAI) and pressure augmentation index (PAI) and have hypothesized that late systolic flow augmentation (FA) in the common carotid artery (CCA), accelerated by wave reflection, causes CMD in subjects with stiffened arteries (Stroke. 2006). To validate this hypothesis under challenge, we investigated the effects of nitroglycerin (NG) on the FA in the CCA. Methods: We recorded pressure and flow velocity waveforms simultaneously in the CCA of nine subjects with coronary heart disease aged 44–72 years before and after sublingual NG (0.3mg). Measurements were taken at baseline and every minute after NG for 8min. Results: Effects of NG reached plateau at 4min and maintained to end of the study. With a little change in brachial diastolic blood pressure (−3mmHg, p= 0.02) flow physiology assessments, for which constant crosssectional area, temperature and intravascular volume in the studied artery are pre-requisites. Methods: Four baboons were anaesthetised and femoral vascular access obtained. A Doppler sensing 0.014 in. FloWireTM and a temperature and pressure sensing 0.014 in.PressureWireTMwereplaced inasegmental lower lobe artery. Selective angiograms, vdopp and pressures were obtained at baseline and at increasing normal saline (NS) infusion rates and boluses. Intravascular temperatures were also recorded. Results: There was no change in vdopp in response to increasing NS infusion rates (25.6± 7.8, 25± 8, 24.8± 7 cm/s at 0, 5 & 15mL/min respectively (p= 0.5)), or boluses (29± 1, 28.3± 0.6, 28.3± 1.5, 28.3± 0.6 cm/s at 0, 2, 5 and 8ml respectively (p= 0.8)). There was no change in vessel diameter with NS infusions or boluses (p= 0.9 & 0.4 respectively). Similarly, there was no change in intravascular temperature (AT vs. left pulmonary artery temperature; 0.02± 0.02, 0.02± 0.02 ◦C at distal and proximal segmental pulmonary artery respectively (p= 0.1)). Conclusions: Segmental pulmonary artery vdopp and Tmn can be reliably obtained using specialised sensor guidewires. Constant vessel cross-sectional area, temperature and volume are maintained under varying haemodynamic loading, thus facilitating accurate pulmonary flow assessments using such guidewires in and heart rate (+2.9 beats/min, p= 0.002), FA [late systolic peak flow velocity – end diastolic flow velocity (Ved)] decreased from 19.4± 1.8 cm/min to 11.5± 1.7 cm/min (averaged value during 4 to 8min), FAI [FA/(peak systolic flowvelocity-Ved)] from59.9± 3.5%to39.8± 3.9%,andPAI from 30.9± 2.6% to 11.2± 4.5% (all, p< 0.0001). Correlation of FAI and PAI was maintained after NG. Conclusions: The present study confirmed the functional relation betweenpressurewave reflection and late systolic flow augmentation in the CCA. Measurement of FAI may provide a gauge of risk for cerebral microvascular disease and expose a new therapeutic strategy against stroke.