Losartan increases NO release in afferent arterioles during regression of l-NAME-induced renal damage

Inhibition of nitric oxide synthesis (NOS) induces hypertension and heavy proteinuria. Renal structure and function have shown striking improvement after interventions targeting ANG II or endothelin (ET) receptors in rats recovering after long-term NOS inhibition. To search for mechanisms underlying losartan-assisted regression of renal disease in rodents, we measured NO release and contractility to ET in afferent arterioles (AAs) from Sprague-Dawley rats recovering for 2 wk after 4 wk of NG-nitro-l-arginine methyl ester treatment. Losartan administration during the recovery period decreased blood pressure (113 ± 4 vs. 146 ± 5 mmHg, P < 0.01), reduced protein/creatinine ratio more (proteinuria decrease: Δ1,836 ± 214 vs. Δ1,024 ± 180 mg/mmol, P < 0.01), and normalized microvascular hypertrophy (AA media/lumen ratio: 1.74 ± 0.05 vs. 2.09 ± 0.08, P < 0.05) compared with no treatment. In diaminofluorescein-FM-loaded AAs from losartan-treated animals, NO release (% of baseline) was increased compared with untreated animals after stimulation with 10−7 M ACh (118 ± 4 vs. 90 ± 7%, t = 560 s, P < 0.001) and 10−9 M ET (123 ± 4 vs. 101 ± 5%, t = 560 s, P < 0.001). There was also a blunted contractile response to 10−7 M ET in AAs from losartan-treated animals compared with untreated animals (Δ4.01 ± 2.9 vs. Δ14.6 ± 1.7 μm, P < 0.01), which disappeared after acute NOS inhibition (Δ10.7 ± 3.7 vs. Δ12.5 ± 2.9 μm, not significant). Contractile dose responses to ET (10−9, 10−8, 10−7 M) were enhanced by NOS inhibition and blunted by exogenous NO (10−2 mM S-nitroso- N-acetyl-penicillamine) in losartan-treated but not in untreated vessels. Reducing blood pressure similar to losartan with hydralazine did not improve AA hypertrophy, ET-induced contractility, ET-induced NO release, and NO sensitivity. In conclusion, blockade of the local action of ANG II improved endothelial function in AAs, a mechanism that is likely to contribute to the beneficial effects of AT1aR antagonism during the recovery of renal function after long-term NOS inhibition in rats.

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Proximal tubule microvilli remodeling and albuminuria in the Ren2 transgenic rat

AJP Renal Physiology ◽

10.1152/ajprenal.00252.2006 ◽

2007 ◽

Vol 292 (2) ◽

pp. F861-F867 ◽

Cited By ~ 17

Author(s):

Melvin R. Hayden ◽

Nazif A. Chowdhury ◽

Shawna A. Cooper ◽

Adam Whaley-Connell ◽

Javad Habibi ◽

...

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

Systolic Blood Pressure ◽

Proximal Tubule ◽

Structural Damage ◽

Kidney Tissue ◽

Proximal Tubule Cell ◽

Ang Ii ◽

Sprague Dawley ◽

Sprague Dawley Rats

TG(mRen2)27 (Ren2) transgenic rats overexpress the mouse renin gene, with subsequent elevated tissue ANG II, hypertension, and nephropathy. The proximal tubule cell (PTC) is responsible for the reabsorption of 5–8 g of glomerular filtered albumin each day. Excess filtered albumin may contribute to PTC damage and tubulointerstitial disease. This investigation examined the role of ANG II-induced oxidative stress in PTC structural remodeling: whether such changes could be modified with in vivo treatment with ANG type 1 receptor (AT1R) blockade (valsartan) or SOD/catalase mimetic (tempol). Male Ren2 (6–7 wk old) and age-matched Sprague-Dawley rats were treated with valsartan (30 mg/kg), tempol (1 mmol/l), or placebo for 3 wk. Systolic blood pressure, albuminuria, N-acetyl-β-d-glucosaminidase, and kidney tissue malondialdehyde (MDA) were measured, and ×60,000 transmission electron microscopy images were used to assess PTC microvilli structure. There were significant differences in systolic blood pressure, albuminuria, lipid peroxidation (MDA and nitrotyrosine staining), and PTC structure in Ren2 vs. Sprague-Dawley rats (each P < 0.05). Increased mean diameter of PTC microvilli in the placebo-treated Ren2 rats ( P < 0.05) correlated strongly with albuminuria ( r2 = 0.83) and moderately with MDA ( r2 = 0.49), and there was an increase in the ratio of abnormal forms of microvilli in placebo-treated Ren2 rats compared with Sprague-Dawley control rats ( P < 0.05). AT1R blockade, but not tempol treatment, abrogated albuminuria and N-acetyl-β-d-glucosaminidase; both therapies corrected abnormalities in oxidative stress and PTC microvilli remodeling. These data indicate that PTC structural damage in the Ren2 rat is related to the oxidative stress response to ANG II and/or albuminuria.

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Abstract 114: K+ Rich Diet During Angiotensin II Hypertension Reduces Renal Na-Cl Cotransporter and Phosphorylation, but Not Blood Pressure

Hypertension ◽

10.1161/hyp.66.suppl_1.114 ◽

2015 ◽

Vol 66 (suppl_1) ◽

Author(s):

Luciana C Veiras ◽

Jiyang Han ◽

Donna L Ralph ◽

Alicia A McDonough

Keyword(s):

Blood Pressure ◽

Urine Volume ◽

Weight Ratio ◽

Distal Tubule ◽

Reduce Blood Pressure ◽

Ang Ii ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

K Secretion ◽

Pressure Natriuresis

During Ang II hypertension distal tubule Na-Cl Cotransporter (NCC) abundance and its activating phosphorylation (NCCp), as well as Epithelial Na+ channels (ENaC) abundance and activating cleavage are increased 1.5-3 fold. Fasting plasma [K+] is significantly lower in Ang II hypertension (3.3 ± 0.1 mM) versus controls (4.0 ± 0.1 mM), likely secondary to ENaC stimulation driving K+ secretion. The aim of this study was to test the hypothesis that doubling dietary K+ intake during Ang II infusion will lower NCC and NCCp abundance to increase Na+ delivery to ENaC to drive K+ excretion and reduce blood pressure. Methods: Male Sprague Dawley rats (225-250 g; n= 7-9/group) were treated over 2 weeks: 1) Control 1% K diet fed (C1K); 2) Ang II infused (400 ng/kg/min) 1% K diet fed (A1K); or 3) Ang II infused 2% K diet fed (A2K). Blood pressure (BP) was determined by tail cuff, electrolytes by flame photometry and transporters’ abundance by immunoblot of cortical homogenates. Results: As previously reported, Ang II infusion increased systolic BP (from 132 ± 5 to 197 ± 4 mmHg), urine volume (UV, 2.4 fold), urine Na+ (UNaV, 1.3 fold), heart /body weight ratio (1.23 fold) and clearance of endogenous Li+ (CLi, measures fluid volume leaving the proximal tubule, from 0.26 ± 0.02 to 0.51 ± 0.01 ml/min/kg) all evidence for pressure natriuresis. A2K rats exhibited normal plasma [K+] (4.6 ± 0.1 mM, unfasted), doubled urine K+ (UKV, from 0.20 to 0.44 mmol/hr), and increased CLi (to 0.8 ± 0.1 ml/min/kg) but UV, UNaV, cardiac hypertrophy and BP were unchanged versus the A1K group. As expected, NCC, NCCpS71 and NCCpT53 abundance increased in the A1K group to 1.5 ± 0.1, 2.9 ± 0.5 and 2.8 ± 0.4 fold versus C1K, respectively. As predicted by our hypothesis, when dietary K+ was doubled (A2K), Ang II infusion did not activate NCC, NCCpS71 nor NCCpT53 (0.91 ± 0.04, 1.3 ± 0.1 and 1.6 ± 0.2 fold versus C1K, respectively). ENaC subunit abundance and cleavage increased 1.5 to 3 fold in both A1K and A2K groups; ROMK was unaffected by Ang II or dietary K. In conclusion, evidence is presented that stimulation of NCC during Ang II hypertension is secondary to K+ deficiency driven by ENaC stimulation since doubling dietary K+ prevents the activation. The results also indicate that elevation in BP is independent of NCC activation

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Abstract 2468: Is the LV Reverse Remodeling Imparted by Aortic Valve Replacement for Severe Aortic Stenosis Durable? A Cardiovascular MRI Study sponsored by the American Heart Association

Circulation ◽

10.1161/circ.116.suppl_16.ii_543-b ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Robert W Biederman ◽

James A Magovern ◽

Saundra Grant ◽

Ronald Williams ◽

June Yamrozik ◽

...

Keyword(s):

Aortic Valve ◽

Aortic Stenosis ◽

Aortic Valve Replacement ◽

Severe Aortic Stenosis ◽

Structure And Function ◽

Reverse Remodeling ◽

Beneficial Effects ◽

And Function ◽

Surgically Induced

Background In patients with severe aortic stenosis (AS), long-term data tracking surgically induced beneficial effects of afterload reduction on reverse LV remodeling are not available. Echocardiographic data is available short term, but in limited fashion beyond one year. Cardiac MRI (CMR) offers the ability to track changes in LV metrics with small numbers due to its inherent high spatial resolution and low variability. Hypothesis We hypothesize that progressive changes following aortic valve replacement (AVR) are detectable by CMR and changes in LV structure and function, triggered by AVR, continue for an extended period following AVR. Methods Ten patients (67±12 yrs, 6 female) with severe, but compensated AS, underwent CMR pre-AVR and post AVR at 6±2mo, 1yr±2mo, 4yrs±5mo. LV mass index (LVMI), LV geometry, volumetrics and EF were measured (GE, EXCITE 1.5T, Milwaukee, WI). A Kruskall-Wallis one-way ANOVA was performed. Results All 10 pts survived AVR and underwent CMR at the 4-year time point (40 total time points). LVMI markedly decreased at 6 months (157±42 to 134±32g/m 2 , p<0.005) and continued to trend down at 4 yrs (127±32g/m 2 ). Similarly, EF increased pre to post AVR (55±22 to 65±11%, (p<0.05)) and continued trending upward, remaining stable at years 1–4 (66±11 vs. 65±9%). LVEDV index, initially high pre AVR, normalized post AVR (83±30 to 68±11ml/m 2 , p<0.05) trending even lower by yr 4 (66±10 ml/m 2 ). LV stroke volume increased rapidly from pre to post AVR (40±11 to 44±7ml) continuing to increase at 4 yrs (49±14ml, p=0.3). Most importantly, LVMI/volume, a 3D measure of LV geometry, remained unchanged initially but over 4 yrs markedly improved (1.07±0.2 to 0.94±0.24, p<0.05) all paralleling improvements in NYHA (3.2±1.0 to 1.5±1.1, p<0.05). Conclusion After the initial beneficial effects imparted by AVR in severe AS patients, there are, as expected, marked improvements in LV reverse remodeling. We have shown, via CMR, that surgically induced benefits to LV structure and function, including favorable alterations in LV geometry, are durable and, unexpectedly, show continued improvement past 4 years concordant with sustained improved clinical status. This supports down regulation of both mRNA and MMP activity acutely and robust suppression long term.

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Abstract 15839: Effect of Serotonin Neuron Depletion on Arterial Blood Pressure Regulation in Young Rats

Circulation ◽

10.1161/circ.130.suppl_2.15839 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Jennifer Magnusson ◽

Kevin Cummings

Keyword(s):

Blood Pressure ◽

Arterial Blood Pressure ◽

Recovery Period ◽

Sudden Infant Death ◽

Sudden Infant ◽

Sprague Dawley ◽

Baroreflex Control ◽

Hypoxic Conditions ◽

Arterial Blood

Infants dying of Sudden Infant Death Syndrome (SIDS) have reduced brainstem serotonin (5-hydroxytryptamine, 5-HT) where some cases die following episodes of severe bradycardia and hypoxemia. The specific role of central 5-HT in resting arterial blood pressure (BP) and on baroreflex sensitivity during neonatal life has not been studied. In adult animals, systemic depletion of 5-HT increases BP with no effect on heart rate (HR) and reduces the sensitivity of the baroreflex. Other studies have also shown that a loss of central 5-HT beginning in embryogenesis reduces resting BP and HR in adulthood. Based on these reports, we hypothesized that loss of brainstem 5-HT neurons in the neonatal period would reduce baseline BP and HR as well as reduce baroreflex gain. To test this, we utilized 3-week old Sprague Dawley rats treated centrally with 5,7-dihydroxytryptamine (5,7-DHT, n=4; ~120 ug in saline, i.c.v.), a chemical that is toxic to serotonergic neurons. Littermate controls were injected with saline (CTRL, n=5, ~3ul, i.c.v.). We measured BP with a femoral artery catheter. HR was derived from BP. Following a recovery period, we measured resting variables for 15 minutes and then injected phenylephrine (PE; 3mg/kg s.c.) followed by sodium nitroprusside (SNP; 2.5mg/kg s.c.), separated by 15 minutes, to induce pressor or depressor responses, respectively. For both responses, baroreflex gain was calculated as the [[Unable to Display Character: ∆]]HR at the maximum [[Unable to Display Character: ∆]]BP following drug injection. We found that a loss of 5-HT neurons did not alter baseline BP (p>0.05) but did reduce baseline HR when compared to control littermates (p<0.02). 5-HT neuron deficiency tended to reduce baroreflex gain in response to PE (CTRL: -2.756 ± 0.483 beats/mmHg; 5,7-DHT: -1.499 ± 0.348 beats/mmHg; p=0.058), but not SNP (CTRL: -2.408 ± 0.351 beats/mmHg; 5,7-DHT: -3.316 ± 1.214 beats/mmHg; p>0.05). Our data indicate that brainstem 5-HT maintains resting HR, and is involved in baroreflex control of HR in response to hypertensive stimuli. Reduced brainstem 5-HT may predispose an infant to SIDS via altered autonomic control of BP and HR. The role of 5-HT in BP regulation during hypoxic conditions remains to be elucidated.

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Abstract P053: Enhanced Exercise Capacity By Muscadine Grape Extract Treatment Is Only Evident In Older Hypertensive Female Rats And Is Independent Of Blood Pressure

Hypertension ◽

10.1161/hyp.76.suppl_1.p053 ◽

2020 ◽

Vol 76 (Suppl_1) ◽

Author(s):

Nildris Cruz Diaz ◽

A'ja V Duncan ◽

Wayne Graham ◽

Brian Westwood ◽

Patricia E. Gallagher ◽

...

Keyword(s):

Blood Pressure ◽

Exercise Capacity ◽

Physical Performance ◽

Term Treatment ◽

Female Rats ◽

Sprague Dawley ◽

Grape Extract ◽

Long Term Treatment ◽

Muscadine Grape

Physical performance and systolic blood pressure (SBP) during aging in normotensive female Sprague-Dawley (SD) and hypertensive (mRen2)27 transgenic rats were assessed following long-term treatment with a Muscadine Grape Extract (MGE, Piedmont Research and Development Corp). MGE was administered at a dose of 0.2 mg/mL in the drinking water starting at 14 weeks (wks) of age with an endpoint at 70 wks of age (total time of treatment of 56 wks). At 20-, 40- and 70-wks of age, physical performance (exercise capacity in seconds and workload in grams - meters) was determined using a treadmill at a velocity of 17 cm/second with a 5% incline. SBP was determined by tail-cuff plethysmography in trained rats. There were no significant differences in physical performance between SD and (mRen2)27 female rats at any age despite the higher SBP in the (mRen2)27 rats at all ages. Long-term treatment with MGE had no significant effect on physical performance or SBP in SD rats at any age. In contrast, MGE treatment markedly increased exercise capacity (40 wks: 1615 ± 166 vs 4943 ± 442 seconds, p<0.01, n = 4-9; 70 wks: 2520 ± 374 vs 4117 ± 245 seconds, p<0.01, n = 4-8) and workload (40 wks: 4579 ± 490 vs 14730 ± 1353 grams - meters, p<0.01, n = 4-9; 70 wks: 8338 ± 1340 vs 13659 ± 933 grams - meters, p<0.01, n = 4-8) at the later ages in female (mRen2)27 rats, while there was no effect on SBP (20 wks: 167 ± 4 vs 173 ± 4 mm Hg, n = 4-6; 40 wks: 177 ± 8 vs 170 ± 7 mm Hg, n = 6-7; 70 wks:154 ± 6 vs 172 ± 6 mm Hg, n = 5) at any age. These data suggest that MGE treatment is effective in improving physical performance only in hypertensive female rats and may be independent of changes in blood pressure. The benefit of MGE in the older hypertensive female may reflect reductions in vascular stiffness and oxidative stress. Support: Chronic Disease Research Fund, Hypertension & Vascular Research Center

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Impact of angiotensin II-mediated stimulation of sodium transporters in the nephron assessed by computational modeling

AJP Renal Physiology ◽

10.1152/ajprenal.00335.2019 ◽

2019 ◽

Vol 317 (6) ◽

pp. F1656-F1668 ◽

Cited By ~ 2

Author(s):

Aurélie Edwards ◽

Alicia A. McDonough

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Ang Ii ◽

Sodium Transporters ◽

Short And Long Term ◽

Physiological Impact ◽

Pressure Natriuresis ◽

Excretion Rates ◽

Volume Output

Angiotensin II (ANG II) raises blood pressure partly by stimulating tubular Na+ reabsorption. The effects of ANG II on tubular Na+ transporters (i.e., channels, pumps, cotransporters, and exchangers) vary between short-term and long-term exposure. To better understand the physiological impact, we used a computational model of transport along the rat nephron to predict the effects of short- and long-term ANG II-induced transporter activation on Na+ and K+ reabsorption/secretion, and to compare measured and calculated excretion rates. Three days of ANG II infusion at 200 ng·kg−1·min−1 is nonpressor, yet stimulates transporter accumulation. The increase in abundance of Na+/H+ exchanger 3 (NHE3) or activated Na+-K+-2Cl− cotransporter-2 (NKCC2-P) predicted significant reductions in urinary Na+ excretion, yet there was no observed change in urine Na+. The lack of antinatriuresis, despite Na+ transporter accumulation, was supported by Li+ and creatinine clearance measurements, leading to the conclusion that 3-day nonpressor ANG II increases transporter abundance without proportional activation. Fourteen days of ANG II infusion at 400 ng·kg−1·min−1 raises blood pressure and increases Na+ transporter abundance along the distal nephron; proximal tubule and medullary loop transporters are decreased and urine Na+ and volume output are increased, evidence for pressure natriuresis. Simulations indicate that decreases in NHE3 and NKCC2-P contribute significantly to reducing Na+ reabsorption along the nephron and to pressure natriuresis. Our results also suggest that differential regulation of medullary (decrease) and cortical (increase) NKCC2-P is important to preserve K+ while minimizing Na+ retention during ANG II infusion. Lastly, our model indicates that accumulation of active Na+-Cl− cotransporter counteracts epithelial Na+ channel-induced urinary K+ loss.

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Abolition of long-term vascular influence of renin-angiotensin system

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1990.259.2.h543 ◽

1990 ◽

Vol 259 (2) ◽

pp. H543-H553

Author(s):

R. D. Randall ◽

B. G. Zimmerman

Keyword(s):

Blood Pressure ◽

Vascular Tissue ◽

Renin Angiotensin System ◽

Ace Inhibition ◽

Ang Ii ◽

Flow Measurements ◽

Angiotensin System ◽

Renin Angiotensin ◽

Normal Controls

Rabbits were bilaterally nephrectomized for 24 h or received an angiotensin-converting enzyme (ACE) inhibitor chronically (5 days) before an acute experiment. Conductance responses to sympathetic nerve stimulation (SNS) (0.25, 0.75, and 2.25 Hz) and norepinephrine (NE) administration (0.2, 0.6, and 1.8 micrograms ia) were determined from simultaneous blood pressure and iliac blood flow measurements. Conductance responses to SNS were significantly reduced in nephrectomized (44, 26, and 20%) and chronic ACE inhibition (39, 31, and 24%) groups compared with normal controls, whereas conductance responses to NE were unchanged. Continuous infusion of angiotensin II (ANG II) for 24 h restored the depressed responses to SNS in nephrectomized and chronic ACE inhibition groups compared with normal controls but did not change conductance responses to NE. Acute ACE inhibition did not affect the conductance responses to SNS or NE compared with controls. Vascular tissue ACE activity was inhibited to a similar degree (50%) in both acute and chronic ACE inhibition groups compared with normal rabbits. Sodium depletion increased the conductance responses to SNS (30 and 24% at 0.25 and 0.75 Hz, respectively), but responses to NE were not affected. Chronic ACE inhibition significantly attenuated the conductance responses to SNS and slightly decreased responses to NE in sodium-depleted rabbits. Thus, in the anesthetized rabbit, the renin-angiotensin system potentiates the effect of SNS, presumably by ANG II acting at a prejunctional site, and this effect of ANG II appears to be long term in nature. Therefore, the renin-angiotensin system exerts a physiological role in the control of blood pressure in addition to the ability of this system to support arterial pressure in pathophysiological states.

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Norepinephrine-evoked salt-sensitive hypertension requires impaired renal sodium chloride cotransporter activity in Sprague-Dawley rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00514.2014 ◽

2016 ◽

Vol 310 (2) ◽

pp. R115-R124 ◽

Cited By ~ 12

Author(s):

Kathryn R. Walsh ◽

Jill T. Kuwabara ◽

Joon W. Shim ◽

Richard D. Wainford

Keyword(s):

Blood Pressure ◽

Sodium Chloride ◽

Salt Sensitivity ◽

Dietary Sodium ◽

Ang Ii ◽

Sprague Dawley ◽

Sodium Chloride Cotransporter ◽

Sprague Dawley Rats ◽

Salt Sensitive Hypertension ◽

The Impact

Recent studies have implicated a role of norepinephrine (NE) in the activation of the sodium chloride cotransporter (NCC) to drive the development of salt-sensitive hypertension. However, the interaction between NE and increased salt intake on blood pressure remains to be fully elucidated. This study examined the impact of a continuous NE infusion on sodium homeostasis and blood pressure in conscious Sprague-Dawley rats challenged with a normal (NS; 0.6% NaCl) or high-salt (HS; 8% NaCl) diet for 14 days. Naïve and saline-infused Sprague-Dawley rats remained normotensive when placed on HS and exhibited dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide. NE infusion resulted in the development of hypertension, which was exacerbated by HS, demonstrating the development of the salt sensitivity of blood pressure [MAP (mmHg) NE+NS: 151 ± 3 vs. NE+HS: 172 ± 4; P < 0.05]. In these salt-sensitive animals, increased NE prevented dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide, suggesting impaired NCC activity contributes to the development of salt sensitivity [peak natriuresis to hydrochlorothiazide (μeq/min) Naïve+NS: 9.4 ± 0.2 vs. Naïve+HS: 7 ± 0.1; P < 0.05; NE+NS: 11.1 ± 1.1; NE+HS: 10.8 ± 0.4). NE infusion did not alter NCC expression in animals maintained on NS; however, dietary sodium-evoked suppression of NCC expression was prevented in animals challenged with NE. Chronic NCC antagonism abolished the salt-sensitive component of NE-mediated hypertension, while chronic ANG II type 1 receptor antagonism significantly attenuated NE-evoked hypertension without restoring NCC function. These data demonstrate that increased levels of NE prevent dietary sodium-evoked suppression of the NCC, via an ANG II-independent mechanism, to stimulate the development of salt-sensitive hypertension.

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The Effect of Long-Term Aronia melanocarpa Extract Supplementation on Cognitive Performance, Mood, and Vascular Function: A Randomized Controlled Trial in Healthy, Middle-Aged Individuals

Nutrients ◽

10.3390/nu12082475 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2475

Author(s):

Sanne Ahles ◽

Yala R. Stevens ◽

Peter J. Joris ◽

David Vauzour ◽

Jos Adam ◽

...

Keyword(s):

Blood Pressure ◽

Cognitive Decline ◽

Cognitive Performance ◽

Cognitive Flexibility ◽

Vascular Function ◽

Psychomotor Speed ◽

Middle Aged ◽

Beneficial Effects ◽

Aronia Melanocarpa

Cognitive decline is associated with lifestyle-related factors such as overweight, blood pressure, and dietary composition. Studies have reported beneficial effects of dietary anthocyanins on cognition in older adults and children. However, the effect of anthocyanin-rich Aronia melanocarpa extract (AME) on cognition is unknown. Therefore, this study aimed to determine the effect of long-term supplementation with AME on cognitive performance, mood, and vascular function in healthy, middle-aged, overweight adults. In a randomized double-blind placebo-controlled parallel study, 101 participants either consumed 90 mg AME, 150 mg AME, or placebo for 24 weeks. The grooved pegboard test, number cross-out test, and Stroop test were performed as measures for psychomotor speed, attention, and cognitive flexibility. Mood was evaluated with a visual analogue scale, serum brain-derived neurotrophic factor (BDNF) was determined, and vascular function was assessed by carotid ultrasounds and blood pressure measurements. AME improved psychomotor speed compared to placebo (90 mg AME: change = −3.37; p = 0.009). Furthermore, 150 mg AME decreased brachial diastolic blood pressure compared to 90 mg AME (change = 2.44; p = 0.011), but not compared to placebo. Attention, cognitive flexibility, BDNF, and other vascular parameters were not affected. In conclusion, AME supplementation showed an indication of beneficial effects on cognitive performance and blood pressure in individuals at risk of cognitive decline.

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Impact of obesity on renal structure and function in the presence and absence of hypertension: evidence from melanocortin-4 receptor-deficient mice

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00187.2009 ◽

2009 ◽

Vol 297 (3) ◽

pp. R803-R812 ◽

Cited By ~ 30

Author(s):

Jussara M. do Carmo ◽

Lakshmi S. Tallam ◽

John V. Roberts ◽

Elizabeth L. Brandon ◽

John Biglane ◽

...

Keyword(s):

Blood Pressure ◽

Renal Injury ◽

Salt Sensitivity ◽

Metabolic Abnormalities ◽

Salt Diet ◽

Melanocortin 4 Receptor ◽

Renal Structure ◽

Long Term Impact ◽

And Function

The purpose of this study was to determine the long-term impact of obesity and related metabolic abnormalities in the absence and presence of hypertension on renal injury and salt-sensitivity of blood pressure. Markers of renal injury and blood pressure salt sensitivity were assessed in 52- to 55-wk-old normotensive melanocortin-4 receptor-deficient (MC4R−/−) mice and lean C57BL/6J wild-type (WT) mice and in 22-wk-old MC4R−/− and WT mice made hypertensive by NG-nitro-l-arginine methyl ester (l-NAME) in the drinking water for 8 wk. Old MC4R−/− mice were 60% heavier, hyperinsulinemic, and hyperleptinemic but had similar mean arterial pressure (MAP) as WT mice (115 ± 2 and 117 ± 2 mmHg) on normal salt diet (0.4% NaCl). A high-salt diet (4.0% NaCl) for 12 days did not raise MAP in obese or lean mice [ΔMAP: MC4R (−/−) 4 ± 2 mmHg; WT, 2 ± 1 mmHg]. Obese MC4R−/− mice had 23% greater glomerular tuft area and moderately increased GFR compared with WT mice. Bowman's space, total glomerular area, mesangial matrix, urinary albumin excretion (UAE), renal TGF-β and collagen expression were not significantly different between old MC4R−/− and WT mice. Renal lipid content was greater but renal macrophage count was markedly lower in MC4R−/− than WT mice. Mild increases in MAP during l-NAME treatment (∼16 mmHg) caused small, but greater, elevations in UAE, renal TGF-β content, and macrophage infiltration in MC4R−/− compared with WT mice without significant changes in glomerular structure. Thus despite long-term obesity and multiple metabolic abnormalities, MC4R−/− mice have no evidence of renal injury or salt-sensitivity of blood pressure. These observations suggest that elevations in blood pressure may be necessary for obesity and related metabolic abnormalities to cause major renal injury or that MC4R−/− mice are protected from renal injury by mechanisms that are still unclear.

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