The effect of tumor-associated protein RCAS1 gene silencing on blood pressure and urinary protein excretion in pregnant mouse: a pilot study

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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Evidence that an angiotensin-converting enzyme inhibitor has a different effect on glomerular injury according to the different phase of the disease at which the treatment is started.

Journal of the American Society of Nephrology ◽

10.1681/asn.v541139 ◽

1994 ◽

Vol 5 (4) ◽

pp. 1139-1146

Author(s):

N Perico ◽

S C Amuchastegui ◽

V Colosio ◽

G Sonzogni ◽

T Bertani ◽

...

Keyword(s):

Blood Pressure ◽

Angiotensin Converting Enzyme ◽

Systolic Blood Pressure ◽

Ace Inhibitor ◽

Diabetic Rats ◽

Urinary Protein Excretion ◽

Urinary Protein ◽

Converting Enzyme ◽

Glomerular Injury ◽

Protein Excretion

In rats with streptozotocin-induced diabetes, the effect of an angiotensin-converting enzyme (ACE) inhibitor on the evolution of glomerular injury according to the time at which the treatment is started with respect to the onset of the disease was studied. Three groups of animals were used, a control Group 1 and two groups of diabetic rats treated with insulin (Groups 2 and 3). The latter were monitored until urinary protein excretion reached 40 to 50 mg/24 h (on average, 23 wk after the induction of the diabetes). At this time, Group 2 continued to receive insulin alone, whereas Group 3 was also given the ACE inhibitor moexipril for 8 more wk. Untreated diabetic rats showed a moderate increase in systolic blood pressure that was normalized by moexipril administration. Urinary protein excretion progressively increased during the 8-wk follow-up in untreated diabetics that, at the end of the study, developed moderate glomerular sclerosis. Moexipril treatment lowered urinary protein excretion to a normal range and completely prevented glomerular injury. Three other groups of rats were similarly treated, except that moexipril treatment was started later on (when proteinuria reached 100 to 200 mg/24 h, on average, 32 wk after the induction of diabetes), and were monitored for another 8 wk. Untreated and treated diabetics had comparable blood glucose levels throughout. Systolic blood pressure, significantly increased in untreated diabetic rats, was effectively controlled by moexipril administration.(ABSTRACT TRUNCATED AT 250 WORDS)

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Differential evolution of blood pressure and renal lesions after RAS blockade in Lyon hypertensive rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00620.2001 ◽

2002 ◽

Vol 283 (5) ◽

pp. R1041-R1045 ◽

Cited By ~ 8

Author(s):

Delphine Bertram ◽

Nelly Blanc-Brunat ◽

Jean Sassard ◽

Ming Lo

Keyword(s):

Blood Pressure ◽

Antihypertensive Effect ◽

Enzyme Inhibitor ◽

Renin Angiotensin System ◽

Urinary Protein Excretion ◽

Urinary Protein ◽

Histological Changes ◽

Angiotensin System ◽

Renal Lesions ◽

Protein Excretion

The present work aimed to assess, in Lyon hypertensive (LH) rats, whether an early and prolonged inhibition of the renin-angiotensin system (RAS) could result in a blood pressure (BP) lowering and nephroprotection that persist after its withdrawal. Male LH rats received orally from 3 to 12 wk of age either an angiotensin-converting enzyme inhibitor perindopril at the doses of 0.4 and 3 mg · kg−1· day−1or an AT1receptor antagonist losartan at the dose of 10 mg · kg−1· day−1. BP, histological changes in the kidney, and urinary protein excretion were examined during and 10 wk after cessation of the treatments. Both perindopril and losartan decreased BP, prevented renal lesions, and limited urinary protein excretion. After cessation of the treatment, BP returned to the level of never-treated LH rats in rats having received 3 mg · kg−1· day−1of perindopril while it remained slightly lower in those treated with 0.4 mg · kg−1· day−1of perindopril or with losartan. This lack of marked persistent antihypertensive effect contrasted with a durable decrease in urinary protein excretion and improvement of the renal histological lesions. In conclusion, it is possible to separate the BP-lowering effects of RAS blockade from those on glomerulosclerosis and urinary protein excretion.

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Interleukin-10 reduces inflammation, endothelial dysfunction, and blood pressure in hypertensive pregnant rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00712.2009 ◽

2010 ◽

Vol 298 (3) ◽

pp. R713-R719 ◽

Cited By ~ 67

Author(s):

John H. Tinsley ◽

Sanique South ◽

Valorie L. Chiasson ◽

Brett M. Mitchell

Keyword(s):

Blood Pressure ◽

Endothelial Dysfunction ◽

Systolic Blood Pressure ◽

Interleukin 10 ◽

Urinary Protein Excretion ◽

Urinary Protein ◽

Hypertensive Disorders Of Pregnancy ◽

Endothelin 1 ◽

Protein Excretion ◽

Hypertensive Disorders

Hypertensive disorders of pregnancy are characterized by systemic and placental inflammation; however, treatment for these conditions has remained elusive. We tested whether administration of the anti-inflammatory cytokine interleukin-10 (IL-10) during pregnancy would attenuate the hypertension, endothelial dysfunction, proteinuria, and inflammation seen in pregnant DOCA/saline-treated (PDS) rats. Normal pregnant (NP) rats and PDS were given daily intraperitoneal injections of recombinant IL-10 from gestational day 13 until death on day 20. Systolic blood pressure, aortic endothelium-dependent relaxation responses, and urinary protein excretion were measured on days 13 and 20 of gestation. Fetal number and development, plasma endothelin-1 levels, serum and placental levels of IFNγ and IL-10, and aortic and placental levels of platelet endothelial cell adhesion molecule (PECAM) were assessed on gestational day 20. Systolic blood pressure, aortic endothelial dysfunction, and urinary protein excretion were significantly increased at gestational day 13 in PDS rats. However, all of these were restored to NP levels following IL-10 treatment in PDS rats. IL-10 treatment also significantly increased the number of pups per litter in PDS rats and did not further affect fetal development. The beneficial effects of IL-10 in PDS rats were likely mediated by the decreased plasma levels of endothelin-1, decreased levels of circulating and placental IFNγ, as well as decreased aortic and placental expression of PECAM. These data demonstrate that exogenous IL-10 can normalize blood pressure and endothelial function in pregnancy-induced hypertensive rats and may be beneficial in women with hypertensive disorders of pregnancy.

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A pilot study to relationship between urinary protein excretion and muscle strengthening in patients with acute onset renal disease

Physical Therapy Research ◽

10.1298/ptr.e9939 ◽

2018 ◽

Vol 21 (2) ◽

pp. 59-64 ◽

Cited By ~ 1

Author(s):

Kohji IWAI ◽

Yasuhiko HATANAKA

Keyword(s):

Pilot Study ◽

Renal Disease ◽

Acute Onset ◽

Urinary Protein Excretion ◽

Urinary Protein ◽

Muscle Strengthening ◽

Protein Excretion

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Improvements of renal lesions and function by angiotensin and endothelin receptor antagonism in nitric oxide-deficient rats

Journal of the Renin-Angiotensin-Aldosterone System ◽

10.1177/14703203010020013701 ◽

2001 ◽

Vol 2 (1_suppl) ◽

pp. S211-S216

Author(s):

Jean-Jacques Boffa ◽

Ying Lu ◽

Jean-Claude Dussaule ◽

Christos Chatziantoniou

Keyword(s):

Blood Pressure ◽

Renal Function ◽

Urinary Protein Excretion ◽

Urinary Protein ◽

Plasma Creatinine ◽

Endothelin Receptor ◽

Receptor Antagonists ◽

Protein Excretion ◽

Sclerotic Lesions ◽

Renal Vascular

In previous studies, we have observed that antagonism of angiotensin or endothelin receptors prevented the development of nephroangio- and glomerulo-sclerosis during hypertension by inhibiting collagen I gene synthesis, through a mechanism independent of systemic haemodynamics. The present study investigated whether treatment with angiotensin or endothelin receptor antagonists, given at doses that did not reduce blood pressure, could produce regression of renal sclerotic lesions and improve renal function during hypertension. Hypertension and renal vascular fibrosis were induced in rats by chronic inhibition of NO synthesis using NGnitro-L-arginine methyl ester (L-NAME). Systolic blood pressure gradually increased following L-NAME administration, reaching a plateau of 170 mmHg after four weeks of treatment. At the same time, urinary protein excretion and plasma creatinine concentration were increased ten- and three-fold compared with controls, respectively (p<0.001). This increase was accompanied by the appearance of sclerotic lesions within renal vessels and glomeruli, as evidenced by Masson's trichromic staining (sclerotic index 2.34±0.29 vs. 0.10±0.01 in L-NAME four weeks and control, respectively, p<0.001). Thereafter, the L-NAME treatment was combined with either losartan (an AT1receptor antagonist), bosentan (an ETA/B antagonist), co-treatment with both agents, or vehicle for an additional period of four weeks. Blockade of AT1and/or ETA/B-receptors significantly reduced urinary protein excretion and plasma creatinine levels (p<0.01) and substantially improved renal vascular histology (sclerotic index 1.78±0.13, 1.57±0.22 and 1.85±0.15 respectively, p<0.01, vs. L-NAME eight week) without altering the L-NAME-induced increase of systolic pressure. These data indicate that angiotensin II and endothelin-1 participate in the mechanism(s) of renal vascular fibrosis by increasing extracellular matrix formation. Treatment with their respective receptor antagonists leads to the regression of renal vascular fibrosis and to the improvement of renal function by a common antifibrogenic mechanism that is independent of systemic haemodynamics.

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The Effects of Hydrocortisone on Systemic Arterial Blood Pressure and Urinary Protein Excretion in Dogs

Journal of Veterinary Internal Medicine ◽

10.1111/j.1939-1676.2007.0039.x ◽

2008 ◽

Vol 22 (2) ◽

pp. 273-281 ◽

Cited By ~ 37

Author(s):

S. Schellenberg ◽

M. Mettler ◽

F. Gentilini ◽

R. Portmann ◽

T.M. Glaus ◽

...

Keyword(s):

Blood Pressure ◽

Arterial Blood Pressure ◽

Urinary Protein Excretion ◽

Urinary Protein ◽

Systemic Arterial Blood Pressure ◽

Protein Excretion ◽

Arterial Blood

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Endothelin receptor A blockade reduces proteinuria and vascular hypertrophy in spontaneously hypertensive rats on high-salt diet in a blood-pressure-independent manner

Clinical Science ◽

10.1042/cs103s385s ◽

2002 ◽

Vol 103 (s2002) ◽

pp. 385S-388S ◽

Cited By ~ 6

Author(s):

Jörg TRENKNER ◽

Friedrich PRIEM ◽

Christian BAUER ◽

Hans-Hellmut NEUMAYER ◽

Manfred RASCHAK ◽

...

Keyword(s):

Blood Pressure ◽

Urinary Protein Excretion ◽

Urinary Protein ◽

Hypertensive Rats ◽

Independent Manner ◽

High Salt Diet ◽

Salt Diet ◽

Spontaneously Hypertensive ◽

Protein Excretion ◽

Pressure Independent

The renal endothelin (ET) system is involved in the pathogenesis of kidney fibrosis as well as blood pressure control by regulating tubular sodium excretion. Long-term effects of ETA receptor blockade on blood pressure and kidney function in spontaneously hypertensive rats (SHRs) on a high-salt diet are unknown. We treated SHRs on a 6% (w/v) NaCl sodium diet (SHR-S) for 48 weeks with the ETA antagonist LU 135252 (whose selectivity for ETA is 150 times greater than for ETB) with 10, 30 and 100mg·kg-1·day-1 or placebo. The ETA antagonist had at no time-point any effect on blood pressure. Glomerular filtration rate was normal in SHR-S and not altered by LU 135252. However, urinary albumin excretion was markedly reduced by the ETA antagonist (SHR-S, 145±50mg/day; SHR-S+10mg·kg-1·day-1 LU 135252, 33±11mg/day, P<0.05 versus SHR-S; SHR-S+30mg·kg-1·day-1 LU 135252, 55±16mg/day and SHR-S+100mg·kg-1·day-1 LU 135252, 32±11mg/day, P<0.05 versus SHR-S at both concentrations). Total urinary protein excretion was likewise significantly reduced by treatment with 10mg·kg-1·day-1 LU 135252 (SHR-S, 0.25±0.06g/day; SHR-S+10mg·kg-1·day-1 LU 135252, 0.089±0.01g/day, P<0.05 versus SHR-S). The higher dosages of LU 135252 showed only a trend towards reduction of total urinary protein excretion. Computer-aided image analysis after haematoxylin/eosin and periodic acid-Schiff staining revealed that treatment with 10mg·kg-1·day-1 LU 135252 significantly reduces the media/lumen ratio of intrarenal arteries. Higher dosages of LU 135252 were less effective. Renal matrix protein synthesis in SHR-S was not altered by LU 135252. In conclusion, the renal ET system contributes in a blood-pressure-independent manner to the regulation of urinary protein excretion and renal vascular hypertrophy in SHR-S. Lower doses of the ETA antagonist were more effective, indicating that a potential additional blockade of the ETB receptor using higher doses of LU 135252 seems to oppose the beneficial effects of a sole ETA blockade. Urinary protein excretion is an independent risk factor of chronic renal failure, thus ETA antagonists might be a therapeutic tool to prevent proteinuria-induced chronic renal failure.

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