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

2010 ◽  
Vol 298 (3) ◽  
pp. R713-R719 ◽  
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.

scholarly journals 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.

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)

Office blood pressure is a predictor of aortic elastic properties and urinary protein excretion in subjects with white coat hypertension

2016 ◽  
Vol 203 ◽  
pp. 98-103 ◽  
Author(s):  
Konstantinos Aznaouridis ◽  
Charalambos Vlachopoulos ◽  
Konstantina Masoura ◽  
Panagiota Pietri ◽  
Gregory Vyssoulis ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Elastic Properties ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Office Blood Pressure ◽  
White Coat ◽  
White Coat Hypertension ◽  
Protein Excretion ◽  
Aortic Elastic Properties

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

2010 ◽  
Vol 203 (4) ◽  
pp. 364.e6-364.e12 ◽  
Author(s):  
Ekaterine Tskitishvili ◽  
Hitomi Nakamura ◽  
Yukiko Kinugasa-Taniguchi ◽  
Takeshi Kanagawa ◽  
Koichiro Shimoya ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Pilot Study ◽  
Gene Silencing ◽  
Pregnant Mouse ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Protein Excretion

scholarly journals Periodic Assessment of Antenatal and Post Natal Serum Endothelin-1 (ET-1) and Nitric Oxide (NO) Levels in Hypertensive Disorders of Pregnancy (HDP)

2020 ◽  
Vol 18 (2) ◽  
Author(s):  
Hidayah I ◽  
Tariq A.R. ◽  
N.A. Jamani ◽  
Maizura M.Z.
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Pregnant Women ◽  
Disease Risk ◽  
Chronic Hypertension ◽  
Hypertensive Disorders Of Pregnancy ◽  
Sample Collection ◽  
Endothelin 1 ◽  
Hypertensive Disorders ◽  
Potent Vasoconstrictor

Hypertensive Disorders of Pregnancy (HDP) is an independent risk factor of cardiovascular (CVS) disease with endothelial dysfunction postulated to be the pathophysiology. Endothelin-1 (ET-1), a potent vasoconstrictor, has been identified as a pivotal mediator in HDP. Disturbances in nitric oxide (NO) bioavailability found in endothelial dysfunction may increase susceptibility to cardiovascular diseases such as hypertension. The study aims to determine serial ET-1 and NO levels in patients with HDP and its role in persistent endothelial dysfunction. Thirty-six pregnant women from the following categories (i) normal pregnant women (Control) (ii) chronic hypertension during pregnancy (CH) and (iii) pregnancy induced hypertension (PIH) participated in this study. Blood pressure indices measurements and sample collection were done at antepartum (32 weeks) and postpartum (8 weeks and 12 weeks). ET-1 and serum NO were measured using the Human ET-1 (Endothelin-1) ELISA Kit and Nitric Oxide (total) detection kit respectively. Results: Serum ET-1 was significantly higher in patients with CH (55.3 pg/ml) and PIH (35.6 pg/ml) compared to Control (11.8 pg/ml) during antenatal until 3 months postpartum (CH 38.3 pg/ml, PIH 29.5 pg/ml, Control 1.9 pg/ml). This was accompanied by significantly lower levels of serum NO in HDP patients. Persistently higher than normal levels of ET-1 and lower than normal levels of NO up to 3 months postpartum in patients with history of HDP indicate presence of persistent endothelial dysfunction despite BP normalisation in PIH patients. Long term NO/ET-1 imbalance may account for the increased CVS disease risk.

scholarly journals Leptin Increases Blood Pressure and Markers of Endothelial Activation during Pregnancy in Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Hisham Saleh Ibrahim ◽  
Effat Omar ◽  
Gabrielle Ruth Anisah Froemming ◽  
Harbindar Jeet Singh
Keyword(s):  
Blood Pressure ◽  
Underlying Mechanism ◽  
Endothelial Activation ◽  
Treated Group ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Sprague Dawley ◽  
Protein Excretion ◽  
Sprague Dawley Rats ◽  
Group 1

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.

scholarly journals Postnatal assessment for renal dysfunction in women with hypertensive disorders of pregnancy

2021 ◽  
Author(s):  
Emmanouil Kountouris ◽  
Katherine Clark ◽  
Polly Kay ◽  
Nadia Roberts ◽  
Kate Bramham ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Renal Dysfunction ◽  
Gestational Hypertension ◽  
Chronic Hypertension ◽  
Hypertensive Disorder ◽  
Hypertensive Disorders Of Pregnancy ◽  
Postpartum Visit ◽  
Protein Excretion ◽  
Hypertensive Disorders

Abstract Background Hypertensive disorders of pregnancy are associated with chronic kidney disease. Early detection of renal dysfunction enables implementation of strategies to prevent progression. International guidelines recommend review at 6–8 weeks postpartum to identify persistent hypertension and abnormal renal function, but evidence for the efficacy of this review is limited. Methods All women attending a specialist fetal-maternal medicine clinic for hypertensive disorders of pregnancy (pre-eclampsia, chronic hypertension, gestational hypertension) were invited for a 6–8 weeks postpartum review of their blood pressure and renal function in order to establish the prevalence and independent predictors of renal dysfunction. Renal dysfunction was defined as low estimated Glomerular Filtration Rate (eGFR < 60 ml/min/1.73 m2) or proteinuria (24-h protein excretion > 150 mg or urinary albumin-to-creatinine ratio > 3 mg/mmol). All women attending a specialist clinic for hypertensive disorders were invited for a 6–8 weeks postpartum review of their blood pressure and renal function. Demographics, pregnancy and renal outcomes were prospectively collected. Results Between 2013 and 2019, 740 of 1050 (70.4%) women who had a pregnancy complicated by a hypertensive disorder attended their 6–8 weeks postpartum visit. Renal dysfunction was present in 32% of the total cohort and in 46% and 22% of women with and without pre-eclampsia, respectively. Multivariate logistic regression demonstrated that independent predictors were pre-eclampsia, chronic hypertension, highest measured antenatal serum creatinine, highest measured antenatal 24-h urinary protein, and blood pressure ≥ 140/90 mmHg at the postnatal visit. Conclusions Renal dysfunction was present in one in three women with hypertensive disorders of pregnancy at 6–8 weeks postpartum. This includes women with gestational hypertension and chronic hypertension without superimposed pre-eclampsia, and thus these women should also be offered postnatal review. Graphic abstract

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

2002 ◽  
Vol 283 (5) ◽  
pp. R1041-R1045 ◽  
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.

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

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.

scholarly journals Quantifying Proteinuria in Hypertensive Disorders of Pregnancy

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Sapna V. Amin ◽  
Sireesha Illipilla ◽  
Shripad Hebbar ◽  
Lavanya Rai ◽  
Pratap Kumar ◽  
...  
Keyword(s):  
False Positive Rate ◽  
Urinary Protein ◽  
Hypertensive Disorders Of Pregnancy ◽  
Inclusion Criteria ◽  
Dipstick Test ◽  
Heavy Proteinuria ◽  
Protein Excretion ◽  
Hypertensive Disorders ◽  
Positive Rate ◽  
Urine Dipstick Test

Background.Progressive proteinuria indicates worsening of the condition in hypertensive disorders of pregnancy and hence its quantification guides clinician in decision making and treatment planning.Objective.To evaluate the efficacy of spot dipstick analysis and urinary protein-creatinine ratio (UPCR) in hypertensive disease of pregnancy for predicting 24-hour proteinuria.Subjects and Methods.A total of 102 patients qualifying inclusion criteria were evaluated with preadmission urine dipstick test and UPCR performed on spot voided sample. After admission, the entire 24-hour urine sample was collected and analysed for daily protein excretion. Dipstick estimation and UPCR were compared to the 24-hour results.Results.Seventy-eight patients (76.5%) had significant proteinuria of more than 300 mg/24 h. Dipstick method showed 59% sensitivity and 67% specificity for prediction of significant proteinuria. Area under curve for UPCR was 0.89 (95% CI: 0.83 to 0.95,P<0.001) showing 82% sensitivity and 12.5% false positive rate for cutoff value of 0.45. Higher cutoff values (1.46 and 1.83) predicted heavy proteinuria (2 g and 3 g/24 h, resp.).Conclusion.This study suggests that random urinary protein : creatine ratio is a reliable investigation compared to dipstick method to assess proteinuria in hypertensive pregnant women. However, clinical laboratories should standardize the reference values for their setup.

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