human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: It has long been proposed that the renin-angiotensin system exerts a stimulatory influence on the sympathetic nervous system , including augmentation of central sympathetic outflow and presynaptic facilitation of norepinephrine release from sympathetic nerves . We tested this proposition in 19 patients with essential hypertension , evaluating whether the angiotensin receptor blockers ( ARBs ) eprosartan and losartan had identifiable antiadrenergic properties . This was done in a prospect i ve , r and omized , three-way placebo-controlled study of crossover design . Patients were r and omized to 600 mg of eprosartan daily , 50 mg of losartan daily , or placebo . The treatment period was 4 wk , with 2-wk washout periods . Multiunit firing rates in efferent sympathetic nerves distributed to skeletal muscle vasculature ( muscle sympathetic nerve activity , MSNA ) were measured with microneurography , testing whether ARBs inhibit central sympathetic outflow . In parallel , isotope dilution methodology was used to measure whole body norepinephrine spillover to plasma . Mean blood pressure on placebo was 151/98 mmHg , with both ARBs causing reductions of approximately 11 mmHg systolic and 6 mmHg diastolic pressure , placebo corrected . Both MSNA [ 35 + /- 12 bursts/min ( mean + /- SD ) on placebo ] and whole body norepinephrine spillover [ 366 + /- 247 ng/min ] were unchanged by ARB administration , indicating that the ARBs did not material ly inhibit central sympathetic outflow or act presynaptically to reduce norepinephrine release at existing rates of nerve firing . These findings contrast with the easily demonstrable reduction in sympathetic nervous activity produced by antihypertensive drugs of the imidazoline-binding class , which are known to act within the brain to inhibit sympathetic nervous outflow . We conclude that sympathetic nervous inhibition is not a major component of the blood pressure-lowering action of ARBs in essential hypertension Impaired nitric oxide ( NO ) vasodilation ( endothelial dysfunction ) is associated with obesity and thought to be a factor in the development of hypertension . We previously found that NO synthesis inhibition had similar pressor effects in obese hypertensives compared with healthy control during autonomic blockade , suggesting that impaired NO vasodilation is secondary to sympathetic activation . We tested this hypothesis by determining the effect of autonomic blockade ( trimethaphan 4 mg/min IV ) on NO-mediated vasodilation ( increase in forearm blood flow to intrabrachial acetylcholine ) compared with endothelial-independent vasodilation ( intrabrachial sodium nitroprusside ) in obese hypertensive subjects ( 30<body mass index<40 kg/m2 ) .  Acetylcholine and sodium nitroprusside were given at equipotent doses ( 10 , 30 , and 50 & mgr;g/min and 1 , 2 , and 3 & mgr;g/min , respectively ) to 14 obese subjects ( 49±3.6 years , 34±1 kg/m2 , 165/94±7/6 mm Hg ) , on separate occasions 1 month apart , r and omly assigned . Autonomic blockade increased basal forearm blood flow ( from 3.9±0.7 to 5.2±1.2 mL/100 mL per minute , P=0.078 ) . As expected , NO-mediated vasodilation was blunted on the intact day compared with NO-independent vasodilation ; forearm blood flow increased from 3.6±0.6 to 10.1±1.1 with the highest dose of nitroprusside , but only from 3.7±0.4 to 7.2±0.8 mL/100 mL per minute with the highest dose of acetylcholine , P<0.05 . In contrast , forearm blood flow responses to acetylcholine  were restored by autonomic blockade and were no longer different to nitroprusside ( from 6.2±1.1 to 11.4±1.6 mL/100 mL per minute and from 5.2±0.9 to 12.5±0.9 , respectively , P=0.58 ) . Our results support the concept that sympathetic activation contributes to the impairment in NO-mediated vasodilation seen in obesity-associated hypertension and provides further rationale to explore it as a therapeutic target Renal sympathetic denervation ( RDN ) is under investigation as a treatment option in patients with resistant hypertension ( RH ) . Determinants of arterial compliance may , however , help to predict the BP response to therapy . Aortic distensibility ( AD ) is a well-established parameter of aortic stiffness and can reliably be obtained by CMR . This analysis sought to investigate the effects of RDN on AD and to assess the predictive value of pre-treatment AD for BP changes . We analyzed data of 65 patients with RH included in a multicenter trial .  RDN was performed in all participants . A st and ardized CMR protocol was utilized at baseline and at 6-month follow-up . AD was determined as the change in cross-sectional aortic area per unit change in BP . Office BP decreased significantly from 173/92 ± 24/16 mmHg at baseline to 151/85 ± 24/17 mmHg ( p < 0.001 ) 6 months after RDN . Maximum aortic areas increased from 604.7 ± 157.7 to 621.1 ± 157.3 mm2 ( p = 0.011 ) . AD improved significantly by 33 % from 1.52 ± 0.82 to 2.02 ± 0.93 × 10−3 mmHg−1 ( p < 0.001 ) . Increase of AD at follow-up was significantly more pronounced in younger patients ( p = 0.005 ) and responders to RDN ( p = 0.002 ) . Patients with high-baseline  AD were significantly younger ( 61.4 ± 10.1 vs. 67.1 ± 8.4 years , p = 0.022 ) . However , there was no significant correlation of baseline AD to response to RDN . AD is improved  after RDN across all age groups . Importantly , these improvements appear to be unrelated to observed BP changes , suggesting that RDN may have direct effects on the central vasculature Background Whether the sympathetic nervous system can directly alter central aortic stiffness remains controversial , mainly because of the difficulty in experimentally augmenting peripheral vasoconstrictor activity without changing blood pressure . Methods and Results To address this limitation , we utilized low‐level cardiopulmonary baroreflex loading and unloading shown previously to alter sympathetic outflow without evoking parallel hemodynamic modulation . Blood pressure and carotid‐femoral aortic pulse wave velocity ( cf‐PWV ) were measured in 32 healthy participants ( 24±2 years ; women : n=15 ) before and during 12‐minute applications of low‐level lower body negative pressure ;  −7 mm Hg ) and lower body positive pressure ; + 7 mm Hg ) , applied in a r and om order . Fibular nerve microneurography was used to collect muscle sympathetic nerve activity ( MSNA ) in a subset ( n=8 ) to confirm peripheral sympathetic responses . During lower body negative pressure , heart rate , blood pressure , stroke volume , cardiac output , and total peripheral resistance were not statistically different ( all P>0.05 ) ; MSNA burst frequency ( + 15 % ; P=0.007 ) , total MSNA ( + 44 % ; P=0.006 ) , and cf‐PWV ( ∆+0.3±0.2 m/s ; P<0.001 ) increased . In total , 28 ( 88 % ) of participants observed an increase in cf‐PWV greater than the baseline typical error of measurement . During lower body positive pressure , heart rate , stroke volume , cardiac output , and total peripheral resistance were not statistically different ( all P>0.05 ) , though blood pressure increased ( P<0.05 ) and pulse pressure decreased ( P=0.01 ) ; MSNA burst frequency ( −4 % ; P=0.37 ) , total MSNA ( −7 % ; P=0.89 ) , and cf‐PWV ( ∆0.0±0.2 m/s ; P=0.68 ) were not statistically different . Conclusions These findings provide evidence that acute elevations in peripheral sympathetic activity can increase central aortic PWV  in young participants independent of a change in distending or pulsatile blood pressure or heart rate Background : Recent research efforts on bariatric surgery have focused on metabolic and diabetes mellitus resolution . R and omized trials design ed to assess the impact of bariatric surgery in patients with obesity and hypertension are needed . Methods : In this r and omized , single-center , nonblinded trial , we included patients with hypertension ( using ≥2 medications at maximum doses or > 2 at moderate doses ) and a body mass index between 30.0 and 39.9 kg/m2 . Patients  were r and omized to Roux-en-Y gastric bypass plus medical therapy or medical therapy alone . The primary end point was reduction of ≥30 % of the total number of antihypertensive medications while maintaining systolic and diastolic blood pressure < 140 mm Hg and 90 mm Hg , respectively , at 12 months . Results : We included 100 patients ( 70 % female , mean age 43.8±9.2 years , mean body mass index 36.9±2.7 kg/m2 ) , and 96 % completed follow-up .  Reduction of ≥30 % of the total number of antihypertensive medications while maintaining controlled blood pressure occurred in 41 of 49 patients from the gastric bypass group ( 83.7 % ) compared with 6 of 47 patients ( 12.8 % ) from the control group with a rate ratio of 6.6 ( 95 % confidence interval , 3.1–14.0 ; P<0.001 ) . Remission of hypertension was present in 25 of 49 ( 51 % ) and 22 of 48 ( 45.8 % ) patients r and omized to gastric bypass , considering office and 24-hour ambulatory blood pressure monitoring , respectively , whereas no patient su bmi tted to medical therapy was free of antihypertensive drugs at 12 months . A post hoc analysis for the primary end point considering the SPRINT ( Systolic Blood Pressure Intervention Trial ) target reached consistent results , with a rate ratio of 3.8 ( 95 % confidence interval , 1.4–10.6 ; P=0.005 ) . Eleven patients ( 22.4 % ) from the gastric bypass group and none in the control group were able to achieve SPRINT levels without antihypertensives . Waist circumference , body mass index , fasting plasma glucose , glycohemoglobin , low-density lipoprotein cholesterol , triglycerides , high-sensitivity C-reactive protein , and 10-year Framingham risk score were lower in the gastric bypass than in the control group . Conclusions : Bariatric surgery represents an effective strategy for blood pressure control in a broad population of patients with obesity and hypertension . Clinical Trial Registration : URL : https:// clinical trials.gov . Unique identifier : NCT01784848 Objective The increase in blood pressure that accompanies the obese state is almost invariably associated with alterations in metabolism ( insulin resistance and dyslipidaemia ) and the neurohumoral profile ( activation of the renin – angiotensin system , sympathetic overactivity ) , which potentiate the cardiovascular risk associated with hypertension . However , debate remains as to the antihypertensive drug on which treatment of obesity-related hypertension should be based . The CROSS ( C and esartan Role on Obesity and on Sympathetic System ) study was undertaken to examine the antihypertensive , neuroadrenergic , and metabolic effects of an angiotensin II receptor blocker in comparison with a diuretic in obese hypertensive individuals . Methods In 127 obese hypertensive individuals aged 50.7 ± 5.1 years ( mean ± SD ) , we measured clinic blood pressure , heart rate , plasma glucose , and insulin at rest and during an oral glucose load before and 12 weeks after treatment with either c and esartan cilexetil ( 8–16 mg once daily ) or hydrochlorothiazide ( HCTZ , 25–50 mg once daily ) , administered orally in accordance with a double-blind , r and omized , placebo-controlled , two-parallel-groups study design . Insulin sensitivity was expressed as insulin resistance index ( IRI ) , calculated as the ratio of the area under the curve ( AUC ) for glucose to that for insulin . In a subgroup of patients , measurements also included direct microneurographic recording of muscle sympathetic nerve activity ( MSNA ) in the peroneal nerve . Results C and esartan cilexetil caused a significant ( P < 0.01 ) reduction in both mean blood pressure ( from 114.2 ± 5.1 to 99.6 ± 6.0 mmHg ) and MSNA ( from 51.0 ± 12.3 to 40.4 ± 12.5 bursts per 100 heart beats ) , and a significant ( P < 0.02 ) increase in insul 
    Output:
    
agent
This indicates that even in the absence of metabolic abnormalities , overweight and obesity are not innocuous , perhaps because the traditional cardiovascular risk factors are either not present early or remain undetected using routine clinical assessment .
This raises the concept that early or sub clinical organ damage assessment s may be better at identifying subjects who are more likely to progress to develop cardiovascular disease .
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: It has long been proposed that the renin-angiotensin system exerts a stimulatory influence on the sympathetic nervous system , including augmentation of central sympathetic outflow and presynaptic facilitation of norepinephrine release from sympathetic nerves . We tested this proposition in 19 patients with essential hypertension , evaluating whether the angiotensin receptor blockers ( ARBs ) eprosartan and losartan had identifiable antiadrenergic properties . This was done in a prospect i ve , r and omized , three-way placebo-controlled study of crossover design . Patients were r and omized to 600 mg of eprosartan daily , 50 mg of losartan daily , or placebo . The treatment period was 4 wk , with 2-wk washout periods . Multiunit firing rates in efferent sympathetic nerves distributed to skeletal muscle vasculature ( muscle sympathetic nerve activity , MSNA ) were measured with microneurography , testing whether ARBs inhibit central sympathetic outflow . In parallel , isotope dilution methodology was used to measure whole body norepinephrine spillover to plasma . Mean blood pressure on placebo was 151/98 mmHg , with both ARBs causing reductions of approximately 11 mmHg systolic and 6 mmHg diastolic pressure , placebo corrected . Both MSNA [ 35 + /- 12 bursts/min ( mean + /- SD ) on placebo ] and whole body norepinephrine spillover [ 366 + /- 247 ng/min ] were unchanged by ARB administration , indicating that the ARBs did not material ly inhibit central sympathetic outflow or act presynaptically to reduce norepinephrine release at existing rates of nerve firing . These findings contrast with the easily demonstrable reduction in sympathetic nervous activity produced by antihypertensive drugs of the imidazoline-binding class , which are known to act within the brain to inhibit sympathetic nervous outflow . We conclude that sympathetic nervous inhibition is not a major component of the blood pressure-lowering action of ARBs in essential hypertension Impaired nitric oxide ( NO ) vasodilation ( endothelial dysfunction ) is associated with obesity and thought to be a factor in the development of hypertension . We previously found that NO synthesis inhibition had similar pressor effects in obese hypertensives compared with healthy control during autonomic blockade , suggesting that impaired NO vasodilation is secondary to sympathetic activation . We tested this hypothesis by determining the effect of autonomic blockade ( trimethaphan 4 mg/min IV ) on NO-mediated vasodilation ( increase in forearm blood flow to intrabrachial acetylcholine ) compared with endothelial-independent vasodilation ( intrabrachial sodium nitroprusside ) in obese hypertensive subjects ( 30<body mass index<40 kg/m2 ) .  Acetylcholine and sodium nitroprusside were given at equipotent doses ( 10 , 30 , and 50 & mgr;g/min and 1 , 2 , and 3 & mgr;g/min , respectively ) to 14 obese subjects ( 49±3.6 years , 34±1 kg/m2 , 165/94±7/6 mm Hg ) , on separate occasions 1 month apart , r and omly assigned . Autonomic blockade increased basal forearm blood flow ( from 3.9±0.7 to 5.2±1.2 mL/100 mL per minute , P=0.078 ) . As expected , NO-mediated vasodilation was blunted on the intact day compared with NO-independent vasodilation ; forearm blood flow increased from 3.6±0.6 to 10.1±1.1 with the highest dose of nitroprusside , but only from 3.7±0.4 to 7.2±0.8 mL/100 mL per minute with the highest dose of acetylcholine , P<0.05 . In contrast , forearm blood flow responses to acetylcholine  were restored by autonomic blockade and were no longer different to nitroprusside ( from 6.2±1.1 to 11.4±1.6 mL/100 mL per minute and from 5.2±0.9 to 12.5±0.9 , respectively , P=0.58 ) . Our results support the concept that sympathetic activation contributes to the impairment in NO-mediated vasodilation seen in obesity-associated hypertension and provides further rationale to explore it as a therapeutic target Renal sympathetic denervation ( RDN ) is under investigation as a treatment option in patients with resistant hypertension ( RH ) . Determinants of arterial compliance may , however , help to predict the BP response to therapy . Aortic distensibility ( AD ) is a well-established parameter of aortic stiffness and can reliably be obtained by CMR . This analysis sought to investigate the effects of RDN on AD and to assess the predictive value of pre-treatment AD for BP changes . We analyzed data of 65 patients with RH included in a multicenter trial .  RDN was performed in all participants . A st and ardized CMR protocol was utilized at baseline and at 6-month follow-up . AD was determined as the change in cross-sectional aortic area per unit change in BP . Office BP decreased significantly from 173/92 ± 24/16 mmHg at baseline to 151/85 ± 24/17 mmHg ( p < 0.001 ) 6 months after RDN . Maximum aortic areas increased from 604.7 ± 157.7 to 621.1 ± 157.3 mm2 ( p = 0.011 ) . AD improved significantly by 33 % from 1.52 ± 0.82 to 2.02 ± 0.93 × 10−3 mmHg−1 ( p < 0.001 ) . Increase of AD at follow-up was significantly more pronounced in younger patients ( p = 0.005 ) and responders to RDN ( p = 0.002 ) . Patients with high-baseline  AD were significantly younger ( 61.4 ± 10.1 vs. 67.1 ± 8.4 years , p = 0.022 ) . However , there was no significant correlation of baseline AD to response to RDN . AD is improved  after RDN across all age groups . Importantly , these improvements appear to be unrelated to observed BP changes , suggesting that RDN may have direct effects on the central vasculature Background Whether the sympathetic nervous system can directly alter central aortic stiffness remains controversial , mainly because of the difficulty in experimentally augmenting peripheral vasoconstrictor activity without changing blood pressure . Methods and Results To address this limitation , we utilized low‐level cardiopulmonary baroreflex loading and unloading shown previously to alter sympathetic outflow without evoking parallel hemodynamic modulation . Blood pressure and carotid‐femoral aortic pulse wave velocity ( cf‐PWV ) were measured in 32 healthy participants ( 24±2 years ; women : n=15 ) before and during 12‐minute applications of low‐level lower body negative pressure ;  −7 mm Hg ) and lower body positive pressure ; + 7 mm Hg ) , applied in a r and om order . Fibular nerve microneurography was used to collect muscle sympathetic nerve activity ( MSNA ) in a subset ( n=8 ) to confirm peripheral sympathetic responses . During lower body negative pressure , heart rate , blood pressure , stroke volume , cardiac output , and total peripheral resistance were not statistically different ( all P>0.05 ) ; MSNA burst frequency ( + 15 % ; P=0.007 ) , total MSNA ( + 44 % ; P=0.006 ) , and cf‐PWV ( ∆+0.3±0.2 m/s ; P<0.001 ) increased . In total , 28 ( 88 % ) of participants observed an increase in cf‐PWV greater than the baseline typical error of measurement . During lower body positive pressure , heart rate , stroke volume , cardiac output , and total peripheral resistance were not statistically different ( all P>0.05 ) , though blood pressure increased ( P<0.05 ) and pulse pressure decreased ( P=0.01 ) ; MSNA burst frequency ( −4 % ; P=0.37 ) , total MSNA ( −7 % ; P=0.89 ) , and cf‐PWV ( ∆0.0±0.2 m/s ; P=0.68 ) were not statistically different . Conclusions These findings provide evidence that acute elevations in peripheral sympathetic activity can increase central aortic PWV  in young participants independent of a change in distending or pulsatile blood pressure or heart rate Background : Recent research efforts on bariatric surgery have focused on metabolic and diabetes mellitus resolution . R and omized trials design ed to assess the impact of bariatric surgery in patients with obesity and hypertension are needed . Methods : In this r and omized , single-center , nonblinded trial , we included patients with hypertension ( using ≥2 medications at maximum doses or > 2 at moderate doses ) and a body mass index between 30.0 and 39.9 kg/m2 . Patients  were r and omized to Roux-en-Y gastric bypass plus medical therapy or medical therapy alone . The primary end point was reduction of ≥30 % of the total number of antihypertensive medications while maintaining systolic and diastolic blood pressure < 140 mm Hg and 90 mm Hg , respectively , at 12 months . Results : We included 100 patients ( 70 % female , mean age 43.8±9.2 years , mean body mass index 36.9±2.7 kg/m2 ) , and 96 % completed follow-up .  Reduction of ≥30 % of the total number of antihypertensive medications while maintaining controlled blood pressure occurred in 41 of 49 patients from the gastric bypass group ( 83.7 % ) compared with 6 of 47 patients ( 12.8 % ) from the control group with a rate ratio of 6.6 ( 95 % confidence interval , 3.1–14.0 ; P<0.001 ) . Remission of hypertension was present in 25 of 49 ( 51 % ) and 22 of 48 ( 45.8 % ) patients r and omized to gastric bypass , considering office and 24-hour ambulatory blood pressure monitoring , respectively , whereas no patient su bmi tted to medical therapy was free of antihypertensive drugs at 12 months . A post hoc analysis for the primary end point considering the SPRINT ( Systolic Blood Pressure Intervention Trial ) target reached consistent results , with a rate ratio of 3.8 ( 95 % confidence interval , 1.4–10.6 ; P=0.005 ) . Eleven patients ( 22.4 % ) from the gastric bypass group and none in the control group were able to achieve SPRINT levels without antihypertensives . Waist circumference , body mass index , fasting plasma glucose , glycohemoglobin , low-density lipoprotein cholesterol , triglycerides , high-sensitivity C-reactive protein , and 10-year Framingham risk score were lower in the gastric bypass than in the control group . Conclusions : Bariatric surgery represents an effective strategy for blood pressure control in a broad population of patients with obesity and hypertension . Clinical Trial Registration : URL : https:// clinical trials.gov . Unique identifier : NCT01784848 Objective The increase in blood pressure that accompanies the obese state is almost invariably associated with alterations in metabolism ( insulin resistance and dyslipidaemia ) and the neurohumoral profile ( activation of the renin – angiotensin system , sympathetic overactivity ) , which potentiate the cardiovascular risk associated with hypertension . However , debate remains as to the antihypertensive drug on which treatment of obesity-related hypertension should be based . The CROSS ( C and esartan Role on Obesity and on Sympathetic System ) study was undertaken to examine the antihypertensive , neuroadrenergic , and metabolic effects of an angiotensin II receptor blocker in comparison with a diuretic in obese hypertensive individuals . Methods In 127 obese hypertensive individuals aged 50.7 ± 5.1 years ( mean ± SD ) , we measured clinic blood pressure , heart rate , plasma glucose , and insulin at rest and during an oral glucose load before and 12 weeks after treatment with either c and esartan cilexetil ( 8–16 mg once daily ) or hydrochlorothiazide ( HCTZ , 25–50 mg once daily ) , administered orally in accordance with a double-blind , r and omized , placebo-controlled , two-parallel-groups study design . Insulin sensitivity was expressed as insulin resistance index ( IRI ) , calculated as the ratio of the area under the curve ( AUC ) for glucose to that for insulin . In a subgroup of patients , measurements also included direct microneurographic recording of muscle sympathetic nerve activity ( MSNA ) in the peroneal nerve . Results C and esartan cilexetil caused a significant ( P < 0.01 ) reduction in both mean blood pressure ( from 114.2 ± 5.1 to 99.6 ± 6.0 mmHg ) and MSNA ( from 51.0 ± 12.3 to 40.4 ± 12.5 bursts per 100 heart beats ) , and a significant ( P < 0.02 ) increase in insul 
    Output:
    