Abstracts From the 36th Annual Scientific Meeting of the HBPRCA

Abstract

HomeHypertensionVol. 65, No. 5Abstracts From the 36th Annual Scientific Meeting of the HBPRCA Free AccessAbstractPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessAbstractPDF/EPUBAbstracts From the 36th Annual Scientific Meeting of the HBPRCA Originally published1 May 2015https://doi.org/10.1161/HYP.0000000000000022Hypertension. 2015;65:e25–e44HBPCRA Oral PresentationsCONTRIBUTION OF THE AREA POSTREMA TO THE INCREASED CARDIAC SYMPATHETIC NERVE ACTIVITY IN OVINE HEART FAILUREAbukar Y, Ramchandra R, May CNThe Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, AustraliaBackground: Heart failure (HF) is associated with an increase in cardiac sympathetic nerve activity (CSNA), which is directly linked to mortality in HF patients. The mechanisms responsible for the elevated CSNA remain unclear. Previous studies indicate that the area postrema (AP), a circumventricular organ in the brainstem, plays a role in the control of sympathetic nerve activity. We hypothesized that the elevated CSNA in HF is mediated by the AP and lesioning this region would reduce the increased CSNA in sheep with HF.Aims: To determine the effect of sham lesion or lesion of the AP on CSNA and hemodynamics in conscious sheep with HF.Methods: Studies were conducted in 2 groups of sheep with pacing-induced HF: sham (n=6) and AP lesion (n=6) sheep. Mean arterial blood pressure (MAP), heart rate (HR) and CSNA were recorded simultaneously in conscious sheep at least 4 days after surgery.Results: Heart failure was associated with a significant decrease in ejection fraction (from 74±2 % to 38±1 %; P<0.001), which was similar in both groups. There was a significant reduction in CSNA burst incidence in the AP lesion group compared with the sham group (45±10 and 89±3 bursts/100 heartbeats, respectively; P<0.01).Conclusions: In sheep with HF, the group with lesion of the AP had a significantly lower CSNA compared with the sham group. These data suggest that the AP plays a role in setting the detrimental high levels of CSNA in HF.G PROTEIN-COUPLED ESTROGEN RECEPTOR SIGNALING IMPROVES STROKE OUTCOME IN FEMALE MICEBroughton BRS, Jansen GL, Sobey CGDepartment of Pharmacology, Monash University, Clayton, Victoria, AustraliaBackground: Estrogen has been assumed to provide neuroprotection following stroke entirely via classical estrogen receptors. Interestingly, there is recent evidence that activation of a novel G protein-coupled estrogen receptor (GPER) with the selective ligand G-1 can improve stroke outcome in ovariectomized mice. However, it remains to be determined if the neuroprotection provided by endogenous estrogen occurs via GPER signaling.Aims: To test if the selective GPER antagonist G-15 worsens stroke outcome and to examine whether tamoxifen, a clinically approved GPER agonist, provides neuroprotection post-stroke.Methods: To address the first aim, intact female C57Bl6 mice were treated i.p. with G-15 (300 μg/kg, n=7) or vehicle (dimethyl sulfoxide, n=8) 1 h prior to 0.5 h middle cerebral artery occlusion (MCAO). To address the second aim, ovariectomized mice were treated i.p. with tamoxifen (10 μg/kg, n=8), vehicle (dimethyl sulfoxide, n=7), or a combination of tamoxifen and G-15 (n=5) 1 h prior to MCAO. In addition, T cell or neutrophil infiltration into the ischemic hemisphere was examined using CD3 or myeloperoxidase immunohistochemistry, respectively.Results: After 24 h, intact female mice treated with G-15 showed worsened functional outcomes and increased infarct damage compared with vehicle. Furthermore, immunohistochemistry showed a significant increase in neutrophils, but not T lymphocytes in the ischemic hemisphere of G-15-treated mice. Tamoxifen-treated mice had significantly improved functional outcomes and ~60% smaller infarct volume (P<0.05) compared to vehicle. The neuroprotective effects of tamoxifen were blocked in the presence of G-15. Immunohistochemistry revealed that tamoxifen limited the infiltration of T lymphocytes and neutrophils within the ischemic hemisphere.Conclusions: These results suggest that in females, GPER activation contributes to estrogen-mediated neuroprotection following stroke, and that tamoxifen can improve stroke outcome following surgical menopause.EFFECTS OF ANTI-HYPERTENSIVE TREATMENT ON FUNCTIONAL AND STRUCTURAL COMPONENTS OF LARGE ARTERY STIFFNESS AND RETINAL VESSEL DIAMETERS IN A RODENT MODEL OF TYPE I DIABETESButlin Ma, Salum Eb, Golzan SMa, Graham SLa, Kaals Jb, Kampus Pb, Avolio APaaAustralian School of Advanced Medicine, Macquarie University, Sydney, New South Wales, Australia;bDepartment of Cardiology, University of Tartu, EstoniaBackground: Diabetes is associated with cardiovascular risk, increased arterial stiffness, and ocular diseases. Whether large artery stiffness is independently associated with diabetes per se or concomitant hypertension is currently unknown.Aims: To determine whether artery stiffness is independently associated with diabetes or is associated concomitantly with hypertension.Methods: Male, Wistar rats (6 weeks of age) were divided into control (n=8), control with anti-hypertensive treatment (telmisartan, 10 mg/kg/day, n=8), induced diabetes (intraperitoneal streptozotocin, 50 mg/kg, confirmed by blood glucose measurement, n=12) and diabetes with anti-hypertensive treatment (n=12). At 18 weeks, rats were anaesthetized (urethane, 1.3 g/kg) and aortic pulse wave velocity (aPWV, aortic stiffness) was measured invasively across a full range of physiological arterial pressure (intravenous phenylephrine, sodium nitroprusside, 30 μg/kg/min). Retinal artery and venous diameters were measured using a custom microscope/camera assembly. Passive (elastin, collagen) and active (endothelial, smooth muscle function) components of aortic vessel stiffness were quantified using tensile testing and myography.Results: Conscious, systolic blood pressure was high in both control and diabetic animals (142±16 and 132±22 mm Hg, respectively) compared to control and diabetic animals on anti-hypertensive therapy (105±11 and 119±14 mm Hg; P<0.01). Diabetic animals had marginally but significantly lower aPWV across all pressures. Anti-hypertensive treatment decreased aPWV within the low pressure range and increased aPWV within the high pressure range for both controls and diabetic animals. This resulted in increased pressure dependency of aPWV with anti-hypertensive treatment. Retinal venous diameters were greater with diabetes. Anti-hypertensive therapy increased retinal venous diameters but decreased arterial diameters. There was no difference in aortic endothelial dependent or independent vasorelaxation. Sensitivity to phenylephrine (vasoconstriction) was less in diabetic animals (P<0.05). Anti-hypertensive therapy caused a rightward shift in the aortic stress-strain curve (P<0.001).Conclusions: Diabetes appeared to have a small but positive effect on arterial stiffness when studied independently of blood pressure. However, high blood pressure decreased the artery’s ability to respond to acute pressure changes, possibly due to remodelling of passive aortic wall components. Retinal venous diameters were greater with diabetes, with anti-hypertensive therapy having different effects on the retinal arteries and veins.PREDICTION OF HEART FAILURE BY SERUM AMINO-TERMINAL-PRO-B-TYPE NATRIURETIC PEPTIDE (NT-PROBNP): AN INTERIM ANALYSIS OF THE SCREENING EVALUATION OF THE EVOLUTION OF NEW HEART FAILURE (SCREEN-HF) STUDYCampbell DJa, McGrady Mb, Prior DLa, Coller JMa, Sheil Lb, Boffa Uc, Wolfe Rb, Reid Cb, Krum HbaSt. Vincent’s Institute of Medical Research, Melbourne, Victoria, Australia;bDepartment of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia;cSchool of Medicine, University of Adelaide, Adelaide, South Australia, AustraliaBackground: Serum NT-proBNP level predicts heart failure. The SCREEN-HF study is a community-based cohort study that aims to identify an appropriate threshold NT-proBNP level for stratification of individuals into high and low risk for heart failure.Aim: To assess whether serum NT-proBPN level can predict heart failure risk in an at-risk population.Methods: We recruited people with at least one risk factor for heart failure: age ≥60 years with one or more of self-reported myocardial infarction or other ischemic or valvular heart disease, arrhythmia, cerebrovascular disease, renal impairment, or treatment for hypertension or diabetes for ≥2 years. Exclusion criteria were known heart failure or left ventricular dysfunction on previous cardiac imaging. Blood was collected from all participants at baseline for measurement of electrolytes, creatinine and NT-proBNP. Median age of the 3938 participants (2171 men and 1767 women) was 70 years (interquartile range 65–75), 83% were receiving treatment for hypertension, 18% were diabetic, 23% had ischemic heart disease (IHD), 11% had cerebrovascular disease, 10% had atrial fibrillation (AF), 32% had body mass index (BMI) >30 kg/m2, 7% had obstructive sleep apnoea (OSA), and 23% had glomerular filtration rate <60 mL/min/1.73 m2.Results: At the time of this interim analysis there were 77 cases of incident heart failure (49 men and 28 women) during a median follow-up of 6 years (incidence rate 3.3 per 1000 person years). Relative to NT-proBNP tertile 1, the odds ratio for incident heart failure was 4.0 (95% confidence interval: 1.1–14.4) for tertile 2 and 21.6 (6.8–69.0) for tertile 3. The C-statistic from receiver operating characteristic analysis was 0.81 (0.77–0.86), with similar values for men and women. NT-proBNP >18 pmol/L (the highest 35%) predicted incident heart failure with 80.5% sensitivity, 66.2% specificity, positive predictive value 4.5% and negative predictive value 99.4%. Although age, diabetes, IHD, AF, BMI and OSA were significant predictors of incident heart failure in a multivariable logistic regression model including NT-proBNP, none improved classification of heart failure risk beyond NT-proBNP alone. Among 3046 participants who had echocardiography, NT-proBNP >18 pmol/L predicted left ventricular ejection fraction (LVEF) <45% with 74% sensitivity and LVEF <40% with 79% sensitivity.Conclusions: Serum NT-proBNP level assists stratification of heart failure risk among a community population with risk factors for heart failure. Improved identification of individuals at increased risk of heart failure will enable targeting of preventative therapies.COST-EFFECTIVENESS OF ANGIOTENSIN-CONVERTING ENZYME INHIBITOR-BASED COMPARED TO THIAZIDE DIURETIC-BASED TREATMENT IN AN ELDERLY HYPERTENSIVE POPULATION CONSIDERING DIABETES AS A MAJOR COMORBIDITYChowdhury Ea, Ademi Za,b, Moss Jc, Wing Ld, Reid Ca on behalf of the Second Australian National Blood Pressure Study Management CommitteeaCentre of Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia;bEuropean Centre of Pharmaceutical Medicine, University of Basel, Switzerland, cSchool of Population Health, The University of Adelaide, Adelaide, South Australia, Australia;dDepartment of Clinical Pharmacology, School of Medicine, Flinders University, Adelaide, AustraliaBackground: Cost-effectiveness is an important consideration in choice of type of anti-hypertensive medication.Aim: To examine the cost-effectiveness of angiotensin-converting enzyme inhibitor-based (ACEI) compared to thiazide diuretic-based treatment for hypertension in elderly Australian considering diabetes as a co-morbidity.Methods: We used a cost-utility analysis to estimate the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained. Data were used from the Second Australian National Blood Pressure Study, a randomized clinical trial comparing diuretic-based versus ACEI-based treatment in 6,083 elderly (age ≥ 65 years) hypertensive patients over a median 4.1-year period. For this economic analysis, the total study population was stratified into two groups. Group A was restricted to participants diabetes-free at baseline (n=5,642); and Group B was restricted to participants with pre-existing diabetes mellitus (Type I or Type II) at baseline (n=441). One-way and probabilistic sensitivity analyses were performed to assess the uncertainty around utilities and cost data.Results: For Group A, the ICER was AUD (Australian dollars) 27,698 per QALY gained comparing ACEI-based with diuretic-based treatment. In Group B, ACEI-based treatment was a dominant strategy (both more effective and cost-saving). On sensitivity analysis, the ICERs per QALY gained were always below AUD 50,000 for Group B, whereas for Group A the probability of being below AUD 50,000 was 85%.Conclusions: Although the dispensed price of diuretic-based treatment of hypertension in the elderly is lower, upon considering the potential enhanced likelihood of the development of diabetes in addition to the costs of treating cardiovascular disease, ACEI-based treatment may be a more cost-effective strategy in this population.EFFECT OF A HIGH FAT DIET AND/OR CHRONIC STRESS ON CARDIOVASCULAR REACTIVITY IN MICEGould EAM, Abegaz B, Nguyen-Huu T-P, Moretti JL, Jackson KL, Head GA, Davern PJBaker IDI Heart & Diabetes Institute, Melbourne, Victoria, AustraliaBackground: Chronic exposure to a high fat diet (HFD) causes hypertension and increased activity of the sympathetic nervous system (SNS). Exposure to chronic aversive stress also influences the SNS and areas in the CNS similar to those activated by a HFD. Thus there is potential for an adverse interaction between a HFD and chronic stress on cardiovascular regulation.Aim: To investigate the interaction between a HFD and chronic stress on cardiovascular reactivity in conscious mice.Methods: Male C57Bl6 mice were fed either a normal fat diet (NFD, n=15) or a HFD (n=11) for 10 weeks and then implanted with telemetry probes to record mean arterial pressure (MAP) and heart rate (HR). After recovery mice were divided into non-stressed and chronically stressed groups. The latter involved daily randomized exposure to 60 minutes of restraint and 2 x 30 minutes of dirty cage switch for 3 weeks. The cardiovascular response to acute stress (restraint, dirty cage switch and novel stressors “feeding” and orbital shaker) were examined before and after exposure to chronic stress.Results: After exposure to HFD, BP was elevated compared to NFD mice (106 versus 97 mm Hg, P<0.01), as was HR, but activity was reduced. Exposure to chronic stress reduced BP and HR in both diet groups and reduced BW only in the HFD mice (P<0.05). The pressor and tachycardic response to orbital shaker stress was markedly elevated by chronic stress (+90% and +49%, respectively, P<0.001), as was the response to feeding. HFD attenuated or abolished the chronic stress induced facilitation. By contrast dirty cage switch was reduced and restraint was well maintained after chronic stress. Interestingly, HFD also abolished the habituation induced by chronic stress.Conclusion: HFD-induced hypertension in mice was reduced by exposure to aversive chronic stress. Interestingly, the ability of chronic stress to facilitate pressor responses to novel stressors was abolished by a HFD. Thus there appears to be a mutually beneficial effect on cardiovascular reactivity with the combination of chronic stress and a HFD, presumably involving an interaction within the CNS.ANTI-HYPERTENSIVE TREATMENT AND CEREBRAL BLOOD FLOW IN HUMAN HYPERTENSIONHart ECa, Ratcliffe LEa, Burchell AEb, Nightingale AKc, Wise Rd, Paton JFRaaSchool of Physiology and Pharmacology, University of Bristol, Bristol, UK;bSchool of Clinical Sciences, University of Bristol, Bristol, UK;cCardiology, University Hospitals Bristol NHS Trust and Foundation, Bristol, UK;dCardiff University Brain Research Imaging Centre, Cardiff University, UKBackground: The onset of high blood pressure may be due to poor cerebral circulation. Additionally, hypertension is related to the development of dementia. Previous work suggests that angiotensin converting enzyme inhibitors (ACEi) improve cerebral blood flow and prevent pathological remodelling of the cerebral vessels when administered to young, hypertensive animals.Aim: To measure whether cerebral blood flow was higher in hypertensive humans taking ACEiMethods: The study involved comparison of hypertensive subjects being treated with ACEi (n=14 [9 being men], age; 58±8 years) and hypertensive subjects taking other anti-hypertensive medications (n=12 [7 being men], age 57±6 years), comprising 6 on calcium channel blockers and 6 on angiotensin receptor blockers) and normotensive (NT) participants (n=13, 54±6 years). Blood flow in the left and right internal carotid and vertebral arteries was measured using magnetic resonance phase contrast imaging. Total cerebral blood flow was the sum of the mean blood flow in all vessels. Total cerebral vascular resistance (CVR) was calculated as mean arterial pressure/total flow during the MR scan.Results: Average 24 hour ambulatory day-time systolic and diastolic blood pressures in both treated groups were comparable (139±4/91±4 mm Hg vs. 141±3/92±3 mm Hg) and were higher than systolic pressure in the NT subjects (117±2 mm Hg; P<0.05). The ACEi group had a total cerebral blood flow similar to NT (49±2 vs. 50±2 mL/100 mL/min), whereas the non ACEi group had a lower cerebral blood flow vs. NT (42±2 mL/100mL/min; P<0.05). Importantly, CVR was increased in the non ACEi group vs. the NT group (1.6±0.1 vs. 2.4±0.2 mm Hg•min/L; P<0.05).Conclusion: The present data provide preliminary evidence that ACEi might help to prevent a reduction in cerebral blood flow in hypertensive humans, potentially by preventing a rise in CVR.ROLE OF THE RENAL NERVES IN A CONSCIOUS RABBIT MODEL OF CHRONIC KIDNEY DISEASEHead GAa, Burke SLa, van Rensch LMb, Sata Ya, Lambert GWa, Denton KMb, Schlaich MPaaBaker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia;bDepartment of Physiology, Monash University, Melbourne, Victoria, AustraliaBackground: Chronic kidney disease (CKD) contributes substantially to the global burden of cardiovascular disease. Nearly 1 in 3 Australians is at risk of developing CKD which is associated with activation of the sympathetic nervous system and elevated blood pressure (BP). The renal nerves are likely to play a major role in CKD-induced hypertension since chronic renal injury can stimulate afferent sensory nerve fibres which directly modulate central neuronal circuits and thus sympathetic outflow. We investigated a novel conscious rabbit model of chronic impaired renal function in which quantitative comparisons can be made of sympathetic activity. We determined the role of the renal nerves in the hypertension and altered autonomic reflex function which characterize the 5/6 renal nephrectomy model of CKD.Aim: To determine whether renal nerves play a role in maintaining CKD-induced hypertension.Methods: Chronic renal failure was induced by lesioning 5/6th of the glomerular layer of the renal cortex in one kidney and, after 2 weeks recovery, removing the contralateral kidney. We examined the role of the renal nerves by denervating the kidneys. Blood parameters, BP and renal sympathetic nerve activity (RSNA) and responses to stress (airjet) and hypoxia (10% O2), baroreflexes and noradrenaline spillover were examined after 3 weeks of CKD.Results: Plasma creatinine and urea were 44% and 38% higher in CKD than control rabbits (P<0.001). BP and RSNA were 8% and 33% higher (P<0.001), but total noradrenaline spillover was 32% lower in CKD rabbits (P<0.05). Responses to hypoxia were attenuated by CKD and RSNA baroreflexes were shifted to the higher BP level. Renal denervation reduced RSNA in both CKD and control rabbits (30%), but only lowered BP in controls. Noradrenaline spillover was unaltered by denervation, but RSNA baroreflexes in both groups were shifted downwards so that both maximum and minimum RSNA were reduced. The hypertension to airjet was enhanced in both groups after denervation, but the hypertension to hypoxia was attenuated in the control animals only. Blood parameters were not altered by renal denervation.Conclusion: Our results show that while RSNA is elevated in CKD, there is sympathoinhibition in other beds. Renal denervation did not alter the renal impairment or the hypertension, suggesting that the renal nerves play a minor role in maintaining CKD-induced hypertension in this model of CKD.THE CONTRIBUTION OF OREXIN TO THE NEUROGENIC HYPERTENSION IN BPH/2J MICEJackson KLa, Nguyen-Huu Ta, Stevenson ERa, Davern PJa, Carrive Pb, Head GAaaNeuropharmacology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia;bSchool of Medical Sciences, University of New South Wales, Sydney, New South Wales, AustraliaBackground: Schlager BPH/2J mice are a genetic model of hypertension associated with an overactive sympathetic nervous system (SNS). Orexin is a neuropeptide which can regulate sympathetic activity, blood pressure and stress. Interestingly, levels of orexin precursor mRNA are greater in the hypothalamus of BPH/2J mice compared with normotensive BPN/3J control mice, particularly during the dark period of the 24 hour light cycle when hypertension is at its greatest in these mice.Aim: To determine whether enhanced orexinergic signaling contributes to hypertension in BPH/2J mice.Methods: BPH/2J and BPN/3J mice (n=6–7) were pre-implanted with radiotelemetry probes to measure mean arterial pressure (MAP). The dual orexin receptor 1 and 2 antagonist, almorexant (Actelion Pharmaceuticals Ltd) was administered via intraperitoneal injection (i.p.) and gavage (p.o.). MAP was recorded for 6 hours and compared with baseline values 1 hour before treatment. Mid frequency (0.3–0.5 Hz) MAP power and the depressor response to ganglion blockade were both used as indicators of SNS activity in vehicle and Almorexant (i.p., 100 mg/kg)-treated mice (n=3–4).Results: Administration of almorexant at 100 mg/kg (i.p.) and 300 mg/kg (p.o.) during the dark period of the 24 hour light cycle caused sustained hypotensive responses in BPH/2J mice (–15.1±1.4 and –10.4±1.1 mm Hg, respectively), which were markedly greater than the effect of vehicle administration (~0.5±0.7 mm Hg; P<0.001). By contrast, the responses to almorexant in BPN/3J mice at all doses and routes were comparable with vehicle (P>0.57). During the dark period almorexant attenuated the depressor response to ganglion blockade in both BPH/2J and BPN/3J mice (P<0.007). Almorexant treatment also reduced the mid frequency MAP power in BPH/2J mice (P<0.001), but not BPN/3J mice (P=0.65). During the light period, almorexant (100 mg/kg, i.p.) did not reduce MAP from baseline in either strain, but a moderate pressor effect following vehicle injection was reduced following almorexant treatment (13.3±1.7 mm Hg vs 1.6±2.0 mm Hg, respectively; P<0.001) in BPH/2J mice only.Conclusion: The present results demonstrate that inhibition of orexin 1 and 2 receptors with almorexant delivered either orally or i.p. can reduce BP and SNS activity in BPH/2J mice. These findings suggest that enhanced orexinergic signaling contributes to overactivation of the SNS and hypertension in BPH/2J mice, particularly during the dark period.BARORECEPTOR FUNCTION IS PRESERVED FOLLOWING FIELD STIMULATION OF CAROTID BARORECEPTORS IN NORMOTENSIVE AND HYPERTENSIVE RATSKouchaki Za, Butlin Ma, Georgakopoulos Db, Avolio APaaAustralian School of Advanced Medicine, Macquarie University, Sydney, New South Wales, Australia;aCVRx Inc., Minneapolis, Minnesota, USABackground: Field stimulation of the carotid baroreceptors has been used successfully to induce long-term reduction in blood pressure. However, whether baroreceptor stimulation may affect the short-term blood pressure regulation function of the baroreceptors in normotensive and hypertensive conditions is not well established.Aim: To determine the effect of field stimulation of carotid baroreceptors on blood pressure in normotensive and hypertensive rats.Methods: Male Wistar Kyoto (WKY, n=7) and spontaneously hypertensive rats (SHR, n=7), each 15–19 weeks old, were anesthetized (urethane, 1.3 g/kg) and unilaterally vagotomized. Thoracic and aortic pressure was measured by an intravascular dual catheter tip pressure sensor (Science, 1.6F). Vessel stiffness was quantified by the pulse wave velocity (PWV) between the two pressure sensors. The left carotid artery was exposed and electrical field stimulation was applied to baroreceptors in the proximity of the carotid bifurcation (stimulation frequency 100 Hz, pulse width 0.53 ms, signal amplitude 3–5 v). A bolus of phenylephrine (1.5 μg) was delivered during baseline conditions (no stimulation) and during carotid baroreceptor stimulation to characterize baroreceptor function. Baroreceptor gain was computed as the absolute change in heart rate (HR) with respect to change in mean blood pressure (MAP).Results: Stimulation caused a significant reduction in HR and MAP in both WKY (P=0.034 for HR, P=0.02 for MAP) and SHR (P=0.0007 for HR, P=0.002 for MAP), indicative of sympathetic inhibition. Field stimulation of the carotid baroreceptors did not affect the baroreceptor gain in either group. WKY: gain at baseline (no stimulation), 0.7±0.19 bpm/mm Hg; gain during stimulation, 0.6±0.12 bpm/mm Hg. SHR: gain at baseline (no stimulation), 0.36±0.10 bpm/mm Hg; gain during stimulation, 0.44±0.12 bpm/mm Hg. There was a non-significant trend for reduction in gain in SHR compared to WKY in both baseline and stimulation conditions. PVW did not change significantly with stimulation in both WKY and SHR.Conclusions: Baroreceptor function was preserved during field stimulation of carotid baroreceptors in both WKY and SHR. This provides support for the use of field stimulation of baroreceptors as a means of blood pressure lowering therapy, whereby the acute and transient control of blood pressure in daily life is maintained.INFLAMMASOME ACTIVITY IS ESSENTIAL FOR DEOXYCORTICOSTERONE ACETATE/SALT-INDUCED HYPERTENSION IN MICEKrishnan SMa, Sobey CGa, Kemp-Harper Ba, Chan CTa, Diep Ha, Dowling Jb, Pinai Ab, Mansell Ab, Drummond GRaaDepartment of Pharmacology, Monash University, Melbourne, Victoria, Australia;bCentre of Innate Immunity and Infectious Diseases, Monash Institute of Medical Research, Melbourne, Victoria, AustraliaBackground: Inflammasomes are signaling complexes comprised of a NOD-like receptor protein (NLRP), an adapter protein (ASC) and caspase-1. Inflammasomes detect host-derived danger signals, causing activation of caspase-1, which in turn cleaves the cytokines pro-interleukin (IL)-1β and pro-IL-18 into their active, pro-inflammatory forms. Hypertension is associated with chronic renal inflammation, but the role of the inflammasome in this process is not known.Aims: To investigate whether deoxycorticosterone acetate (DOCA)/salt-induced hypertension in mice is associated with increased expression and/or activation of the inflammasome in the kidney, and assess the impact of inhibition of inflammasome activity on blood pressure (BP) and markers of renal inflammation and fibrosis.Methods and Results: Male C57BL6/J (wild type) and ASC–/– mice were uninephrectomized, implanted with a DOCA pellet (2.4 mg/day, 21 days, s.c.) and had their drinking water replaced with 1% saline (1K/DOCA/salt). Control mice also had a kidney removed but received a placebo pellet and normal drinking water. 1K/DOCA/salt-treated mice had elevated systolic BP (146±4 mm Hg) compared to control mice (115±2 mm Hg; n=13–16; P<0.05). 1K/DOCA/salt-induced hypertension was associated with increased renal mRNA (fold-change vs. control; n=7–9; P<0.05) of inflammasome subunits NLRP3 (2.3±0.2), ASC (2.8±0.6) and pro-caspase-1 (2.6±0.5), and of the cytokine pro-IL-1β (4.0±0.8). Moreover, protein levels of cleaved (active) caspase-1 and IL-1β were increased by 1.6±0.2- and 2.1±0.3-fold, respectively in kidneys of 1K/DOCA/salt vs. control mice (n=6; P<0.05). ASC–/– mice, which lack an active inflammasome complex, displayed blunted hypertensive responses to 1K/DOCA/salt-treatment (140±3 mm Hg) compared to wild types (155±8 mm Hg; n=8–9; P<0.05). ASC–/– mice were also protected from 1K/DOCA/salt-induced increases in renal levels of mRNAs for inflammatory proteins IL-6, IL-17a, CCL2, ICAM-1 and VCAM-1, and accumulation of collagen.Conclusion: Renal inflammation, fibrosis and elevated BP in response to 1K/DOCA/salt-treatment are critically dependent on inflammasome activity, highlighting this signaling complex and its cytokine products as potential therapeutic targets to treat hypertension.INVESTIGATING THE ROLE OF B CELLS IN THE VASCULAR WALL DURING ANGIOTENSIN II-INDUCED HYPERTENSION IN MICELieu Ma, Chan CTa, Sobey CGa, Kyaw TSb, Tipping Pc, Bobik Ab, Toh BHc, Drummond GRaaVascular Biology & Immunopharmacology Group, Department of Pharmacology, Monash University, Clayton, Melbourne, Victoria, Australia;bVascular Biology & Atherosclerosis Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia;cCentre for Inflammatory Diseases, Department of Medicine, Southern Clinical School, Monash University, Clayton, Melbourne, Victoria, AustraliaBackground: Recent studies by our Laboratory suggest that B cell-deficient mice display a blunted hypertensive response to angiotensin (Ang) II. However, the mechanism(s) by which B cells promote hypertension remain to be determined.Aims: (i) To examine whether Ang II-induced hypertension in mice is associated with the accumulation and/or activation of B cells within the vascular wall. (ii) To determine whether these cells represent a source of antibodies, chemokines and/or reactive oxygen species (ROS) duri