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BackgroundTo mitigate the effect of the COVID-19 pandemic, health care systems worldwide have implemented telemedicine technologies to respond to the growing need for health care services during these unprecedented times. In the United Arab Emirates, video and audio consultations have been implemented to deliver health services during the pandemic. ObjectiveThis study aimed to evaluate whether differences exist in physicians’ attitudes and perceptions of video and audio consultations when delivering telemedicine services during the COVID-19 pandemic. MethodsThis survey was conducted on a cohort of 880 physicians from outpatient facilities in Abu Dhabi, which delivered telemedicine services during the COVID-19 pandemic between November and December 2020. In total, 623 physicians responded (response rate=70.8%). The survey included a 5-point Likert scale to measure physician’s attitudes and perceptions of video and audio consultations with reference to the quality of the clinical consultation and the professional productivity. Descriptive statistics were used to describe physicians’ sociodemographic characteristics (age, sex, designation, clinical specialty, duration of practice, and previous experience with telemedicine) and telemedicine modality (video vs audio consultations). Regression models were used to assess the association between telemedicine modality and physicians’ characteristics with the perceived outcomes of the web-based consultation. ResultsCompared to audio consultations, video consultations were significantly associated with physicians’ confidence toward managing acute consultations (odds ratio [OR] 1.62, 95% CI 1.2-2.21; P=.002) and an increased ability to provide patient education during the web-based consultation (OR 2.21, 95% CI 1.04-4.33; P=.04). There was no significant difference in physicians’ confidence toward managing long-term and follow-up consultations through video or audio consultations (OR 1.35, 95% CI 0.88-2.08; P=.17). Video consultations were less likely to be associated with a reduced overall consultation time (OR 0.69, 95% CI 0.51-0.93; P=.02) and reduced time for patient note-taking compared to face-to-face visits (OR 0.48, 95% CI 0.36-0.65; P

We have previously shown that a permanent deficiency in the brain renin-angiotensin system (RAS) may increase the sensitivity of the baroreflex control of heart rate. In this study we aimed at studying the involvement of the brain RAS in the cardiac reactivity to the [beta]-adrenoceptor ([beta]-AR) agonist isoproterenol (Iso). Transgenic rats with low brain angiotensinogen (TGR) were used. In isolated hearts, Iso induced a significantly greater increase in left ventricular (LV) pressure and maximal contraction (+dP/[dt.sub.max]) in the TGR than in the Sprague-Dawley (SD) rats. LV hypertrophy induced by Iso treatment was significantly higher in TGR than in SD rats (in g LV wt/100 g body wt, 0.28 [+ or -] 0.004 vs. 0.24 [+ or -] 0.004, respectively). The greater LV hypertrophy in TGR rats was associated with more pronounced downregulation of [beta]-AR and upregulation of LV [beta]-AR kinase-1 mRNA levels compared with those in SD rats. The decrease in the heart rate (HR) induced by the [beta]-AR antagonist metoprolol in conscious rats was significantly attenuated in TGR compared with SD rats (-9.9 [+ or -] 1.7% vs. - 18.1 [+ or -] 1.5%), whereas the effect of parasympathetic blockade by atropine on HR was similar in both strains. These results indicate that TGR are more sensitive to [beta]-AR agonist-induced cardiac inotropic response and hypertrophy, possibly due to chronically low sympathetic outflow directed to the heart. autonomic nervous system; sympathetic nervous system; [beta]-adrenoreceptor

In this study, we aimed to investigate the adaptation of blood pressure (BP), heart rate (HR), and locomotor activity (LA) circadian rhythms to light cycle shift in transgenic rats with a deficit in brain angiotensin [TGR(ASrAOGEN)]. BP, HR, and LA were measured by telemetry. After baseline recordings (bLD), the light cycle was inverted by prolonging the light by 12 h and thereafter the dark period by 12 h, resulting in inverted dark-light (DL) or light-dark (LD) cycles. Toward that end, a 24-h dark was maintained for 14 days (free-running conditions). When light cycle was changed from bLD to DL, the acrophases (peak time of curve fitting) of BP, HR, and LA shifted to the new dark period in both SD and TGR(ASrAOGEN) rats. However, the readjustment of the BP and HR acrophases in TGR(ASrAOGEN) rats occurred significantly slower than SD rats. The LA acrophases changed similarly in both strains. When light cycle was changed from DL to LD by prolonging the dark period by 12 h, the reentrainment of BP and LA occurred faster than the previous shift in both strains. The readjustment of the BP and HR acrophases in TGR(ASrAOGEN) rats occurred significantly slower than SD rats. In free-running conditions, the circadian rhythms of the investigated parameters adapted in TGR(ASrAOGEN) and SD rats in a similar manner. These results demonstrate that the brain RAS plays an important role in mediating the effects of light cycle shifts on the circadian variation of BP and HR. The adaptive behavior of cardiovascular circadian rhythms depends on the initial direction of light-dark changes. brain renin-angiotensin system; heart rate

Female spontaneously hypertensive rats (SHR) have lower blood pressures than males. The renin-angiotensin system plays an important role in the sexual dimorphism of blood pressure in SHR. The sympathetic nervous system can stimulate renin release, and, therefore, the present study was performed to determine whether the renal sympathetic nerves play a role in the sexual dimorphism of blood pressure in SHR. Male and female SHR underwent bilateral kidney denervation or sham surgery, and, 2 wk later, mean arterial pressure (MAP) and pulse interval were recorded, and baroreflex sensitivity (BRS) was measured by the sequence technique. Left ventricle index (LVI) was also calculated. MAP was higher in sham-operated males than females (182 [+ or -] 5 vs. 169 [+ or -] 4 mmHg; P < 0.01), but, despite the higher MAP in males, LVI was significantly greater in female rats. BRS was not different between sham-operated male and female SHR. Following bilateral renal denervation, MAP was decreased by a similar percentage (8-10%) in males (169 [+ pr -] 2 mmHg) and females (152 [+ or -] 3 mmHg), whereas LVI was reduced only in female SHR. BRS was not altered by renal denervation in either sex. These data indicate that renal nerves play a role in the control of blood pressure in SHR independent of sex, but do not play a role in mediating the sex differences in blood pressure. baroreflex sensitivity; mean arterial pressure; sexual dimorphism; renal denervation

Background: Atherosclerotic carotid intima-media thickness (IMT) may be associated with alterations in the sensitivity of carotid baroreceptors. The aim of this study was to investigate the association between carotid IMT and the autonomic modulation of heart rate variability (HRV). Methods: A total of 101 subjects were enrolled in this prospective observational study. The carotid IMT was determined by duplex ultrasonography. The cardiac autonomic function was determined through HRV measures during the Deep Breathing Test. Linear regression models, adjusted for demographics, comorbidities, body mass index, waist-hip-ratio, and left ventricular ejection fraction were used to evaluate the association between HRV parameters and carotid IMT. Results: Participants had a mean age of 60.4 ± 13.4 years and an estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk score (using the Pooled Cohort Equations) of 16.4 ± 17. The mean carotid media thickness was highest (0.90 ± 0.19 mm) in the first quartile of the standard deviation of all RR intervals (SDNN) (19.7 ± 5.1ms) and progressively declined in each subsequent quartile to 0.82 ± 0.21 mm, 0.81 ± 0.16 mm, and 0.68 ± 0.19 in quartiles 2 (36.5 ± 5.9 ms), 3 (57.7 ± 6.2 ms) and 4 (100.9 ± 22.2ms), respectively. In multivariable adjusted models, there was a statistical significant association between SDNN and carotid IMT (OR -0.002; 95%CI -0.003 to -0.001, p = 0.005). The same significant association was found between carotid IMT and other measures of HRV, including coefficient of variation of RR intervals (CV) and dispersion of points along the line of identity (SD2). Conclusions: In a cohort of individuals at increased cardiovascular risk, carotid IMT as a marker of subclinical atherosclerosis was associated with alterations of HRV indicating an impaired cardiac autonomic control, independently of other cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to identify the most sensitive heart rate and blood pressure variability (HRV and BPV) parameters from a given set of well-known methods for the quantification of cardiovascular autonomic function after several autonomic blockades. Methods: Cardiovascular sympathetic and parasympathetic functions were studied in freely moving rats following peripheral muscarinic (methylatropine), β1-adrenergic (metoprolol), muscarinic + β1-adrenergic, α1-adrenergic (prazosin), and ganglionic (hexamethonium) blockades. Time domain, frequency domain and symbolic dynamics measures for each of HRV and BPV were classified through paired Wilcoxon test for all autonomic drugs separately. In order to select those variables that have a high relevance to, and stable influence on our target measurements (HRV, BPV) we used Fisher's Method to combine the p-value of multiple tests. Results: This analysis led to the following best set of cardiovascular variability parameters: The mean normal beat-to-beat-interval/value (HRV/BPV: meanNN), the coefficient of variation (cvNN = standard deviation over meanNN) and the root mean square differences of successive (RMSSD) of the time domain analysis. In frequency domain analysis the very-low-frequency (VLF) component was selected. From symbolic dynamics Shannon entropy of the word distribution (FWSHANNON) as well as POLVAR3, the non-linear parameter to detect intermittently decreased variability, showed the best ability to discriminate between the different autonomic blockades. Conclusion: Throughout a complex comparative analysis of HRV and BPV measures altered by a set of autonomic drugs, we identified the most sensitive set of informative cardiovascular variability indexes able to pick up the modifications imposed by the autonomic challenges. These indexes may help to increase our understanding of cardiovascular sympathetic and parasympathetic functions in translational studies of experimental diseases. [ABSTRACT FROM AUTHOR]

Objectives: Surgical stress induces alterations on sympathovagal balance that can be determined through assessment of blood pressure variability. Coronary artery bypass graft surgery (CABG) is associated with postoperative respiratory depression. In this study we aimed at investigating ICU blood pressure variability and other perioperative parameters that could predict the nadir of postoperative respiratory function impairment. Methods: This prospective observational study evaluated 44 coronary artery disease patients subjected to coronary artery bypass surgery (CABG) with cardiopulmonary bypass (CPB). At the ICU, mean arterial pressure (MAP) was monitored every 30 min for 3 days.MAPvariabilitywasevaluatedthrough:standarddeviation (SD),coefficient of variation (CV), variation independent of mean (VIM), and average successive variability (ASV). Respiratory functionwasassessed through maximal inspiratory (MIP) and expiratory (MEP) pressures and peak expiratory flow (PEF) determined 1 day before surgery and on the postoperative days 3rd to 7th. Intraoperative parameters (volume of cardioplegia, CPB duration, aortic cross-clamp time, number of grafts) were also monitored. Results: Since, we aimed at studying patients without confounding effects of postoperative complications on respiratory function, we had enrolled a cohort of low risk EuroSCORE (European System for Cardiac Operative Risk Evaluation) with <2. Respiratory parameters MIP, MEP, and PEF were significantly depressed for 4-5 days postoperatively. Of all MAP variability parameters, the ASV had a significant good positive Spearman correlation (rho coefficients ranging from 0.45 to 0.65, p < 0.01) with the 3-day nadir of PEF after cardiac surgery. Also, CV and VIM of MAP were significantly associated with nadir days of MEP and PEF. None of the intraoperative parameters had any correlation with the postoperative respiratory depression. Conclusions: Variability parameters ASV, CV, and VIM of the MAP monitored at ICU may have predictive value for the depression of respiratory function after cardiac surgery as determined by peak expiratory flow and maximal expiratory pressure. [ABSTRACT FROM AUTHOR]

Accumulating evidence indicates that various biological and neuroendocrine circadian rhythms may be disrupted in cardiovascular and metabolic disorders. These circadian alterations may contribute to the progression of disease. Our studies direct to an important role of angiotensin II and melatonin in the modulation of circadian rhythms. The brain renin-angiotensin system (RAS) may modulate melatonin synthesis, a hormone with well-established roles in regulating circadian rhythms. Angiotensin production in the central nervous system may not only influence hypertension but also appears to affect the circadian rhythm of blood pressure. Drugs acting on RAS have been proven effective in the treatment of cardiovascular and metabolic disorders including hypertension and diabetes mellitus (DM). On the other hand, since melatonin is capable of ameliorating metabolic abnormalities in DM and insulin resistance, the beneficial effects of RAS blockade could be improved through combined RAS blocker and melatonin therapy. Contemporary research is evidencing the existence of specific clock genes forming central and peripheral clocks governing circadian rhythms. Further research on the interaction between these two neurohormones and the clock genes governing circadian clocks may progress our understanding on the pathophysiology of disease with possible impact on chronotherapeutic strategies. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of topical application of avosentan (SPP 301), endothelin receptor type A antagonist, on intraocular pressure (IOP) in monkey eyes with laser-induced unilateral glaucoma. Materials and Methods: A multiple-dose study was performed in eight glaucomatous monkey eyes that were topically treated with SPP 301 by applying a 50 µl drop (25 µl × 2) at 9:30 a.m. and 3:30 p.m. for 5 consecutive days at three concentrations (0.003%, 0.03%, or 0.3%). IOP was measured hourly for 6 hrs on each day of the study beginning at 9:30 a.m. for one baseline day, one vehicle-treated day, and treatment days 1, 3, and 5. Results: Twice daily administration of each of the three concentrations of SPP 301 for 5 days significantly ( p < 0.05) reduced IOP. The maximum reduction in IOP occurred 2 or 3 hrs after morning dosing and was 1.8 ± 0.8 (mean ± SEM) mmHg (6%) for 0.003% SPP 301, 4.1 ± 0.7 mmHg (13%) for 0.03% SPP 301, and 7.1 ± 1.3 mmHg (21%) for 0.3% SPP 301. The longest duration of IOP reduction was for 2 hrs with 0.003% SPP 301, and was for at least 6 hrs with 0.03% and 0.3% concentrations. Compared to 0.03% or 0.003% concentrations, 0.3% SPP 301 produced a greater ( p < 0.05) IOP reduction. IOP was reduced in fellow untreated normal eyes 2 hr after morning dosing with 0.3% SPP 301, maximum reduction in IOP (11%) occurred on day 1. Of the eyes treated with 0.3% SPP 301, one eye demonstrated mild conjunctival discharge and one eye was closed for 5 min after dosing. Conclusion: Topically applied SPP 301, an endothelin antagonist, reduced IOP in glaucomatous monkey eyes in a dose-dependent manner. Endothelin antagonists, a novel class of compound, may have potential for the treatment of glaucoma. [ABSTRACT FROM AUTHOR]

Rat models of hypertension, eg, spontaneously hypertensive stroke-prone rats (SHRSP), display reduced angiotensin-converting enzyme 2 (ACE2) mRNA and protein expression compared with control animals. The aim of this study was to investigate the role of ACE2 in the pathogenesis of hypertension in these models. Therefore, we generated transgenic rats on a SHRSP genetic background expressing the human ACE2 in vascular smooth muscle cells by the use of the SM22 promoter, called SHRSP-ACE2. In these transgenic rats vascular smooth muscle expression of human ACE2 was confirmed by RNase protection, real-time RT-PCR, and ACE2 activity assays. Transgene expression leads to significantly increased circulating levels of angiotensin-(1-7), a prominent product of ACE2. Mean arterial blood pressure was reduced in SHRSP-ACE2 compared to SHRSP rats, and the vasoconstrictive response to intraarterial administration of angiotensin II was attenuated. The latter effect was abolished by previous administration of an ACE2 inhibitor. To evaluate the endothelial function in vivo, endothelium-dependent and endothelium-independent agents such as acetylcholine and sodium nitroprusside, respectively, were applied to the descending thoracic aorta and blood pressure was monitored. Endothelial function turned out to be significantly improved in SHRSP-ACE2 rats compared to SHRSP. These data demonstrate that vascular ACE2 overexpression in SHRSP reduces hypertension probably by locally degrading angiotensin II and improving endothelial function. Thus, activation of the ACE2/angiotensin-(1-7) axis may be a novel therapeutic strategy in hypertension. [ABSTRACT FROM AUTHOR]

Kinins play a central role in the modulation of cardiovascular function and in the pathophysiology of inflammation. These peptides mediate their effects by binding to two specific G-protein coupled receptors named B1 and B2. To evaluate the full functional relevance of the kallikrein-kinin system, we generated mice lacking both kinin receptors (B1B2-/-). Because of the dose chromosomal position of both kinin receptor genes, B1B2-/- mice could not be obtained by simple breeding of the single knockout lines. Therefore, we inactivated the B1 receptor gene by homologous recombination in embryonic stem cells derived from B2-deficient animals. The B1B2-/- mice exhibited undetectable levels of mRNAs for both receptors and a lack of response to bradykinin (B2 agonist) and des-Arg9-bradykinin (B1 agonist), as attested by contractility studies with isolated smooth muscle tissues. B1B2-/- mice are healthy and fertile, and no sign of cardiac abnormality was detected. They are normotensive but exhibit a lower heart rate than controls. Furthermore, kinin receptor deficiency affects the pathogenesis of endotoxin-induced hypotension. While blood pressure decreased markedly in wild-type mice and B2-/- and moderately in B1-/- mice after bacterial lipopolysaccharide (LPS) injection, blood pressure remained unchanged in B1B2-/- mice. These results dearly demonstrate a pivotal role of kinins and their receptors in hypotension induced by endotoxemia in mice. [ABSTRACT FROM AUTHOR]

Background: Physical activity (PA) and the consequently lower cardiorespiratory fitness levels in older adults decline with age and are associated with cardiovascular disease events and mortality. In the present study we aimed at evaluating the effectiveness of a 12-week supervised physical training community-based program on cardiovascular risk factors and health-related quality of life (HRQoL) in elderly women.METHODS: An exercise intervention was conducted as a prospective, longitudinal and controlled study in 30 elderly participants. Intervention consisted of an individually designed group-based PA program thrice a week (aerobic exercise, resistance training and stretching exercises for 1 h each time), for a period of 12 weeks. The following cardiovascular risk data were investigated: blood pressure, triglycerides, HDL, glycaemia, body mass index (BMI) and waist circumference. HRQoL was evaluated with the Short Form-36 (SF-36).RESULTS: Mean age was 69 ± 0.9 years, normotensive (63% with controlled hypertension), BMI was 25 ± 0.7 kg/m2 and waist circumference was 89 ± 1.6 cm. The exercise group prevented the significant HDL decrease that occurred in the sedentary group (HDL increase: 2.5 [95%CI -4.4 to 9.4] vs HDL decrease: -9.2 [95%CI -16.2 to -2.2], p< 0.01). There was also a significant improvement in the SF-36 subscales in PA but not sedentary group: physical functioning score (increase of 24.2 [95%CI 11.8 to 36.5] vs. -9.2 [95%CI -21.5 to 3.2], p< 0.001), physical role functioning score (increase of 35.4 [95%CI 12.8 to 58.0] vs. 16.7 [95%CI -6.0 to 39.3], p< 0.01) and general health score (increase of 23.7 [95%CI 36.9 to 10.4] vs. 2.4 [95%CI -10.9 to 15.7], p< 0.001).CONCLUSIONS: This study shows that a 12-week physical training program may significantly improve cardiovascular risk reduction, physical capacity, physical function and general health scores. [ABSTRACT FROM AUTHOR]

Background: The atherosclerotic carotid disease is characterized by thickening of the intima-media of the vascular wall (IMT), which is considered as a reliable predictor of cardiovascular events. The aim of this study was to investigate a relationship between IMT and nonatherosclerotic cardiac and vascular risk factors in postmenopausal women.Methods: Left and right carotid IMT, plaque score and resistive index (common, external and internal carotid RI), left ventricular (LV) wall thickness and ascending aorta diameter were determined by echography.Results: Women’s and men’s age was normally distributed with mean(SD) of 71(11) and 68(11), respectively. Left and right carotid IMTs were strongly correlated to each other (Spearman's r = 0.71 in women and 0.89 in men, p < 0.001). Only the right IMT was correlated with the plaque score at both sexes (Spearman's r = 0.36 in women and 0.37 in men, p = 0.01). The carotid resistive indexes had no significant relationship with the C-IMTs. The LV wall thickness and the ascending aorta diameter had a significantly positive correlation with the right IMT in women (Spearman's r = 0.31 and 0.31, p < 0.05) but not in men. The carotid RIs had a significantly positive association with age in both sexes (Spearman's r ranging between 0.30 and 0.56, p < 0.05). However, right IMT, LV thickness and aortic diameter were positively correlated with age only in women (Spearman's r = 0.33, 0.40 and 0.26 respectively, p < 0.05).Conclusion: These data demonstrate that nonatherosclerotic risk factors are associated with higher IMT in women but not in men. The synergic action of these factors may contribute to a worse carotid deterioration in postmenopausal women. [ABSTRACT FROM AUTHOR]

Objective. Coronary artery bypass graft surgery (CABG) is associated with postoperative respiratory depression. The primary endpoint of this study was the determination whether the blood pressure variability during the intensive care unit (ICU) is correlated with the nadir of postoperative respiratory function impairment.Methods. This prospective study evaluated 44 patients subjected to CABG with cardiopulmonary bypass (CPB). Mean arterial pressure (MAP) was monitored every 30 min for 3 days at the ICU. MAP variability was evaluated through: standard deviation (SD), coefficient of variation (CV), variation independent of mean (VIM), average successive variability (ASV) and SD of ASV. Respiratory function was assessed through maximal inspiratory (MIP) and expiratory (MEP) pressures and expiratory peak flow rate (EPFR) determined 1 day before surgery and on the postoperative days 3rd to 7th.Results. Respiratory parameters MIP, MEP and EPFR were significantly depressed postoperatively for 4, 4 and 5 days respectively. Patient adherence to EPFR monitoring was higher than for MIP and MEP. None of the perioperative parameters (volume of cardioplegia, CPB duration, aortic cross-clamp time, number of grafts) had any correlation with the postoperative respiratory depression. Of all MAP variability parameters, the ASV and SD of ASV had a significant good positive Spearman correlation (rho coefficients ranging from 0.45 to 0.65, p<0.01) with the nadir depression of EPFR for 5 days after cardiac surgery.Conclusion. Variability parameters ASV and SD of ASV of the MAP monitored at ICU may have predictive value for the depression of respiratory function after cardiac surgery as determined by EPFR. [ABSTRACT FROM AUTHOR]

Background: Atherosclerotic intima-media thickening (IMT) of carotid or subclavian artery may be associated with alterations in the sensitivity of carotid and subclavian baroreceptors. This is why we aimed at investigating if IMT is associated with alterations in the autonomic modulation of heart rate variability (HRV).Methods: This was a cross-sectional study with 30 subjects. The atherosclerotic artery IMT was determined by B-mode and duplex ultrasonography. HRV was evaluated through linear (low frequency [LF, ms2], high frequency [HF, ms2], standard deviation (SD) of normal R-R wave intervals [SDNN], square root of the mean of the sum of the squares of differences between adjacent normal R wave intervals [RMSSD]) and nonlinear Poincaré analysis (SD of the points perpendicular to the line-of-identity [SD1, ms]; SD along the line-of-identity [SD2, ms]).Results: A significant negative linear correlation was identified between the IMT of common carotid artery and the HRV indexes that reflects baroreflex and the fluctuations of autonomic tone: LF, Spearman's r = -0.52, 95% CI: -0.75 to -0.19, P = 0.003; SDNN, Spearman's r = -0.57, 95% CI: -0.78 to -0.25, P = 0.001; SD2, Spearman's r = -0.59, 95% CI: -0.79 to -0.28, P = 0.0006. Similar strong negative correlations were found for subclavian IMT. In contrast, there was no relationship between IMT and the HRV indexes related to autonomic tone (HF, LF/HF, RMSSD, SD1, SD1/SD2). The receiver operating characteristic (ROC) sensitivities/specificities/area under curve of SD2 for predicting carotid and subclavian artery IMT were 0.75/0.83/0.81 and 0.70/0.69/0.70, respectively (cutoff values: <32.8 and <42.5, respectively). Identification of atherosclerotic plaque in subclavian artery (IMT > 1.5 mm) was associated with a drastic reduction of SD2 (25.9 [24.3-40.5] vs. 50.2 [38.1-68.7]; data are median and interquartile range values, p = 0.0009), LF (65% lower, p = 0.005) and SDNN (43% lower, p = 0.001).Conclusions: Our data demonstrate that the atherosclerotic carotid and subclavian IMT are associated with an impairment of cardiac autonomic control. The SD2 index of Poincaré plot may be a functional biomarker for subjects at risk for carotid disease and an indicator for ultrasound evaluation. [ABSTRACT FROM AUTHOR]

Abstract: Previous evidence indicates that a balance between inhibitory gabaergic and excitatory angiotensinergic factors in the PVN is important for cardiovascular control. We investigated the cardiovascular response evoked from activation or blockade of GABAA receptors in the paraventricular nucleus (PVN), in transgenic rats with low brain angiotensinogen [TGR(ASrAOGEN)]. Brain Ang II and Ang-(1–7) levels were also determined. In functional experiments, TGR(ASrAOGEN) and Sprague–Dawley rats (SD, control) were anesthetized with urethane and blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded. Brain Ang II and Ang-(1–7) levels were largely reduced in TGR(ASrAOGEN) compared with SD rats. Inhibition of PVN neurons with the GABAA agonist, muscimol (1nmol/100nL), resulted in an attenuated fall in all cardiovascular variables in TGR(ASrAOGEN) compared with SD rats. This difference was particularly pronounced in HR (TGR Mus −23±6bpm vs. −77±9bpm SD Mus; P <0.05) and RSNA (TGR −3±10% vs.−29±8% SD; P <0.05). Furthermore, the sympathetic response evoked by blockade of GABAA receptors in the PVN of TGR(ASrAOGEN) was also largely suppressed. The present data indicate that the sympathetic outflow mediated by PVN neurons under basal conditions is suppressed in TGR(ASrAOGEN) rats corroborating the functional significance of brain angiotensin production in the central regulation of sympathetic output to the cardiovascular system. [Copyright &y& Elsevier]