Resibufogenin Prevents Leptin-Induced Increases in Blood Pressure and Markers of Endothelial Activation During Pregnancy in Sprague Dawley Rats

Raised leptin levels have been reported in the placentae and serum of women with elevated blood pressure and proteinuria during pregnancy. The role of leptin in this however remains unknown. This study investigates the effect of leptin administration on systolic blood pressure (SBP) and proteinuria and serum markers of endothelial activation during pregnancy inSprague Dawley rats. From day 1 of pregnancy, 24 rats were randomised into those given either saline (group 1) or leptin at 60 or 120 μg/kg/body weight/day (groups 2 and 3 resp.). SBP was measured every 5 days and 24-h urinary protein was measured at days 0 and 20 of pregnancy. Animals were euthanised on day 20 of pregnancy, and serum was collected for estimation of E-selectin and ICAM-1. Compared to group 1, SBP during the latter part of the pregnancy was significantly higher in the leptin-treated group (P<0.01). Urinary protein excretion, serum E-selectin, and ICAM-1 were significantly higher in leptin-treated rats (P<0.05). It seems that leptin administration to normotensiveSprague Dawley ratsduring pregnancy significantly increases SBP, urinary protein excretion, and markers of endothelial activation. However, further studies are required to examine the underlying mechanism responsible for this and its relevance to preeclampsia in humans.

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Leptin-induced increase in blood pressure and markers of endothelial activation during pregnancy in Sprague Dawley rats is prevented by resibufogenin, a marinobufagenin antagonist

Reproductive Biology ◽

10.1016/j.repbio.2020.03.004 ◽

2020 ◽

Vol 20 (2) ◽

pp. 184-190 ◽

Cited By ~ 1

Author(s):

Maryam Jameelah Md Hassan ◽

Nor Salmah Bakar ◽

Mardiana Abdul Aziz ◽

Norizan Kamal Basah ◽

Harbindar Jeet Singh

Keyword(s):

Blood Pressure ◽

Endothelial Activation ◽

Sprague Dawley ◽

Sprague Dawley Rats

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Increased superoxide levels in ganglia and sympathoexcitation are involved in sarafotoxin 6c-induced hypertension

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00783.2007 ◽

2008 ◽

Vol 295 (5) ◽

pp. R1546-R1554 ◽

Cited By ~ 8

Author(s):

Melissa Li ◽

Xiaoling Dai ◽

Stephanie Watts ◽

David Kreulen ◽

Gregory Fink

Keyword(s):

Blood Pressure ◽

Sympathetic Innervation ◽

Sympathetic Ganglia ◽

Plasma Norepinephrine ◽

Sprague Dawley ◽

Surgical Ablation ◽

Arterial Blood ◽

Sprague Dawley Rats ◽

Induced Hypertension ◽

Hypertension Development

Endothelin (ET) type B receptors (ETBR) are expressed in multiple tissues and perform different functions depending on their location. ETBR mediate endothelium-dependent vasodilation, clearance of circulating ET, and diuretic effects; all of these should produce a fall in arterial blood pressure. However, we recently showed that chronic activation of ETBR in rats with the selective agonist sarafotoxin 6c (S6c) causes sustained hypertension. We have proposed that one mechanism of this effect is constriction of capacitance vessels. The current study was performed to determine whether S6c hypertension is caused by increased generation of reactive oxygen species (ROS) and/or activation of the sympathetic nervous system. The model used was continuous 5-day infusion of S6c into male Sprague-Dawley rats. No changes in superoxide anion levels in arteries and veins were found in hypertensive S6c-treated rats. However, superoxide levels were increased in sympathetic ganglia from S6c-treated rats. In addition, superoxide levels in ganglia increased progressively the longer the animals received S6c. Treatment with the antioxidant tempol impaired S6c-induced hypertension and decreased superoxide levels in ganglia. Acute ganglion blockade lowered blood pressure more in S6c-treated rats than in vehicle-treated rats. Although plasma norepinephrine levels were not increased in S6c hypertension, surgical ablation of the celiac ganglion plexus, which provides most of the sympathetic innervation to the splanchnic organs, significantly attenuated hypertension development. The results suggest that S6c-induced hypertension is partially mediated by sympathoexcitation to the splanchnic organs driven by increased oxidative stress in prevertebral sympathetic ganglia.

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The Effect of Excess Dietary Sucrose on Growth, Blood Pressure, and Metabolism in Developing Sprague-Dawley Rats

Pediatric Research ◽

10.1203/00006450-199407001-00017 ◽

1994 ◽

Vol 36 ◽

pp. 95-100 ◽

Cited By ~ 33

Author(s):

S Hulman ◽

B Falkner

Keyword(s):

Blood Pressure ◽

Sprague Dawley ◽

Sprague Dawley Rats

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Methylglyoxal, a Reactive Glucose Metabolite, Increases Renin Angiotensin Aldosterone and Blood Pressure in Male Sprague-Dawley Rats

American Journal of Hypertension ◽

10.1093/ajh/hpt281 ◽

2014 ◽

Vol 27 (3) ◽

pp. 308-316 ◽

Cited By ~ 14

Author(s):

Indu Dhar ◽

Arti Dhar ◽

Lingyun Wu ◽

Kaushik M. Desai

Keyword(s):

Blood Pressure ◽

Sprague Dawley ◽

Renin Angiotensin ◽

Sprague Dawley 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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Inhibition of microRNA-429 in the renal medulla increased salt sensitivity of blood pressure in Sprague Dawley rats

Journal of Hypertension ◽

10.1097/hjh.0000000000001373 ◽

2017 ◽

Vol 35 (9) ◽

pp. 1872-1880 ◽

Cited By ~ 4

Author(s):

Qing Zhu ◽

Junping Hu ◽

Lei Wang ◽

Weili Wang ◽

Zhengchao Wang ◽

...

Keyword(s):

Blood Pressure ◽

Renal Medulla ◽

Salt Sensitivity ◽

Sprague Dawley ◽

Sprague Dawley Rats

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Exercise training and its effects with renal hypertensive rats

Journal of Applied Physiology ◽

10.1152/jappl.1985.59.5.1410 ◽

1985 ◽

Vol 59 (5) ◽

pp. 1410-1415 ◽

Cited By ~ 19

Author(s):

K. D. Marcus ◽

C. M. Tipton

Keyword(s):

Blood Pressure ◽

Exercise Training ◽

Capillary Density ◽

Heart Weight ◽

Sprague Dawley ◽

Vo2 Max ◽

Arterial Blood ◽

Sprague Dawley Rats ◽

Resting Blood Pressure ◽

Renal Hypertensive Rats

The influence of endurance training on functional capacity [maximal O2 consumption (VO2 max)], caudal arterial blood pressure, and myocardial capillary density were investigated in normotensive rats and rats made hypertensive using the two-kidney one-clip approach (Goldblatt's hypertension). Male Sprague-Dawley rats were assigned to sham (N: 120–140 mmHg), moderately hypertensive (MH = 0.30-mm clips, 150–170 mmHg), or severely hypertensive (SH = 0.25-mm clips, 190–230 mmHg) groups. Rats designated to be runners (T) were exercised on a motor-driven treadmill equal to 50–70% of their VO2 max values for 8–12 wk. Compared with their nontrained (NT) controls, training was associated with significantly higher VO2 max values (12–15%) and muscle cytochrome-c oxidase activities (33–78%). Resting systolic blood pressure was not significantly changed in the N-and MH-T subgroups; however, it was 20–30 mmHg higher in the SH-T subgroup. Mean absolute heart weight for only the N-T group was significantly heavier than their NT controls. However, the mean predicted heart weights (heart wt = 0.639 X body wt of N-NT + 0.001 g) of the two SH groups were significantly higher than expected. The SH-T group had a lower (11%) subepicardial capillary density mean than its NT control and significantly fewer capillaries in the subendocardial region than the other five subgroups. It was concluded that moderate exercise training appeared to be detrimental to rats with severe hypertension because it increased resting blood pressure and decreased myocardial capillary density, even though it improved their functioning capacity.

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