scholarly journals Chronic hyperleptinemia results in the development of hypertension in pregnant rats

2015 ◽  
Vol 308 (10) ◽  
pp. R855-R861 ◽  
Author(s):  
Ana C. Palei ◽  
Frank T. Spradley ◽  
Joey P. Granger
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Food Intake ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Pregnant Rats ◽  
Ad Libitum ◽  
Factor Α ◽  
Necrosis Factor

Despite the fact that obesity is a major risk factor for preeclampsia (PE), the pathophysiological mechanisms whereby obesity and metabolic factors such as leptin increase this risk are unclear. While human data have shown that hyperleptinemia is associated with PE, the long-term effect of hyperleptinemia on blood pressure during pregnancy is unknown. Thus we tested the hypothesis whether chronic circulating leptin elevations in pregnant rats increase blood pressure and placental factors known to play a role in PE. On gestational day (GD)14, rats were assigned to the normal pregnant group with food intake ad libitum (control), leptin-treated (0.5 μg·kg−1·min−1 ip) pregnant group with food intake ad libitum (pregnant+LEP), and normal pregnant group with food intake adjusted to the food intake of pregnant+LEP rats (pregnant-FR). On GD19, mean arterial pressure (MAP) was assessed and tissues were collected. Serum leptin concentration was elevated in pregnant+LEP compared with control and pregnant-FR (18.0 ± 2.8 vs. 0.8 ± 0.1 vs. 0.3 ± 0.1 ng/ml; P < 0.05), which was associated with increased MAP (121.3 ± 8.1 vs. 102.4 ± 2.4 vs. 101.3 ± 1.8 mmHg; P < 0.05). Food intake and body weight were reduced in pregnant+LEP and pregnant-FR by the end of gestation. Additionally, placentas and fetuses of these groups were lighter than those of control. However, placental expression of tumor necrosis factor-α was significantly greater in pregnant+LEP compared with controls (1.6 ± 0.1 vs. 1.1 ± 0.1 pg/mg; P < 0.05). In conclusion, leptin increases blood pressure and placental tumor necrosis factor-α during pregnancy despite its effect of reducing food intake and body weight, and represents a mechanism whereby obesity can promote the development of hypertension in PE.

Effect of tumor necrosis factor-α inhibitors on ambulatory 24-h blood pressure

2016 ◽  
Vol 26 (1) ◽  
pp. 24-29 ◽  
Author(s):  
Chagai Grossman ◽  
Gil Bornstein ◽  
Avshalom Leibowitz ◽  
Ilan Ben-Zvi ◽  
Ehud Grossman
Keyword(s):  
Blood Pressure ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Tumor Necrosis Factor-α Antagonist Etanercept Decreases Blood Pressure and Protects the Kidney in a Mouse Model of Systemic Lupus Erythematosus

Hypertension ◽  
2010 ◽  
Vol 56 (4) ◽  
pp. 643-649 ◽  
Author(s):  
Marcia Venegas-Pont ◽  
Michaele B. Manigrasso ◽  
Samira C. Grifoni ◽  
Babbette B. LaMarca ◽  
Christine Maric ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Blood Pressure ◽  
Tumor Necrosis Factor ◽  
Mouse Model ◽  
Lupus Erythematosus ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Systemic Lupus ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Tumor necrosis factor-α: regulation of renal function and blood pressure

2013 ◽  
Vol 304 (10) ◽  
pp. F1231-F1242 ◽  
Author(s):  
Vanesa D. Ramseyer ◽  
Jeffrey L. Garvin
Keyword(s):  
Blood Pressure ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Immune Cell ◽  
Organ Damage ◽  
Physiological Status ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Tumor necrosis factor-α (TNF-α) is a pleiotropic cytokine that becomes elevated in chronic inflammatory states such as hypertension and diabetes and has been found to mediate both increases and decreases in blood pressure. High levels of TNF-α decrease blood pressure, whereas moderate increases in TNF-α have been associated with increased NaCl retention and hypertension. The explanation for these disparate effects is not clear but could simply be due to different concentrations of TNF-α within the kidney, the physiological status of the subject, or the type of stimulus initiating the inflammatory response. TNF-α alters renal hemodynamics and nephron transport, affecting both activity and expression of transporters. It also mediates organ damage by stimulating immune cell infiltration and cell death. Here we will summarize the available findings and attempt to provide plausible explanations for such discrepancies.

Tumor necrosis factor-α-angiotensin interactions and regulation of blood pressure

1997 ◽  
Vol 15 (12) ◽  
pp. 1481-1484 ◽  
Author(s):  
Nicholas R. Ferreri ◽  
Yejun Zhao ◽  
Hideki Takizawa ◽  
John C. McGiff
Keyword(s):  
Blood Pressure ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Factor Α ◽  
Regulation Of Blood Pressure ◽  
Necrosis Factor

scholarly journals Central Leptin and Tumor Necrosis Factor-α (TNFα) in Diurnal Control of Blood Pressure and Hypertension

2016 ◽  
Vol 291 (29) ◽  
pp. 15131-15142 ◽  
Author(s):  
Cheng Han ◽  
Wenhe Wu ◽  
Albert Ale ◽  
Min Soo Kim ◽  
Dongsheng Cai
Keyword(s):  
Blood Pressure ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor

Differential expression of uterine NO in pregnant and nonpregnant rats with intrauterine bacterial infection

2001 ◽  
Vol 280 (5) ◽  
pp. R1356-R1363 ◽  
Author(s):  
L. Fang ◽  
B. Nowicki ◽  
C. Yallampalli
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Intrauterine Infection ◽  
Uterine Horn ◽  
No Production ◽  
Pregnant Rats ◽  
Escherichia Coli Infection ◽  
Factor Α ◽  
Necrosis Factor

Previous studies have demonstrated that nitric oxide (NO) is involved in the uterine host defense against bacterial infection. In nonpregnant rats, NO production in the uterus was shown to be lower, and inducible NO synthase (NOS) expression was undetectable. However, studies in pregnant rats show abundant expression of inducible NOS with significant elevation in NO production in the uterus. We have recently reported that intrauterine Escherichia coli infection caused a localized increase in uterine NO production and inducible NOS expression in the nonpregnant rat. In our present study, we examined whether the uterine NO production, NOS expression, and uterine tumor necrosis factor-α protein are increased in pregnant rats with intrauterine pathogenic Escherichia coli infection. Unlike the nonpregnant state, the NO production in the infected uterine horn of pregnant rats was not significantly elevated after bacterial inoculation compared with the contralateral uterine horn. The expression of uterine NOS (types II and III) also did not show significant upregulation in the infected horn. This is in contrast to that in nonpregnant animals, in which type II NOS was induced in the uterus on infection. Moreover, intrauterine infection induced an elevated expression of tumor necrosis factor-α protein in the infected horn both of nonpregnant and of pregnant rats. These data suggest that the sequential stimulation of NOS expression, especially the inducible isoform, and generation of uterine NO are lacking during pregnancy despite an elevated tumor necrosis factor-α after infection. In summary, NO synthesis response may be maximal at pregnancy, and infection may not further induce the NO system. Present studies, together with our previous report that intrauterine infection-induced lethality in pregnancy rats was amplified with the inhibition of NO, suggest that pregnancy is a state predisposed for increased complications associated with intrauterine infection and that the constitutively elevated uterine NO during pregnancy may help contain or even reduce the risk of infection-related complications.

scholarly journals Control of soluble fms-like tyrosine-1 (sFlt-1) production response to placental ischemia/hypoxia: role of tumor necrosis factor-α

2013 ◽  
Vol 304 (2) ◽  
pp. R130-R135 ◽  
Author(s):  
Sydney R. Murphy ◽  
B. Babbette D. LaMarca ◽  
Marc Parrish ◽  
Kathy Cockrell ◽  
Joey P. Granger
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Acute Hypoxia ◽  
Pregnant Rats ◽  
Tnf Α ◽  
Factor Α ◽  
Placental Ischemia ◽  
Necrosis Factor

Although abnormal soluble fms-like tyrosine kinase-1 (sFlt-1) production is thought to be an important factor in the pathogenesis of preeclampsia (PE), the mechanisms that regulate the production of sFlt-1 during PE are unclear. While our laboratory has shown tumor necrosis factor-α (TNF-α) and sFlt-1 to be elevated in pregnant rats in response to placental ischemia, the importance of TNF-α in the regulation of sFlt-1 production is unknown. Therefore, the purpose of this study was to determine the role of TNF-α in mediating the increase in sFlt-1 in response to placental ischemia or hypoxia. Reductions in uterine perfusion pressure in pregnant rats significantly increased plasma levels of sFlt-1 and tended to increase TNF-α, an effect markedly attenuated by pretreatment with a TNF-α inhibitor etanercept (0.4 mg/kg). To further assess chronic interactions between TNF-α and sFlt-1, we examined a chronic effect of TNF-α infusion (50 ng/day) into normal pregnant rats to increase plasma sFlt-1 levels, as well as the effects of acute hypoxia on placental sFlt-1 production in the absence and presence of TNF-α blockade. Placental explants exposed to hypoxic conditions had enhanced TNF-α levels versus normoxic conditions, as well as increased sFlt-1 production. Pretreatment of placental explants with etanercept (15 μM) significantly reduced TNF-α levels in response to hypoxia but did not attenuate sFlt-1 production. These data suggest that while TNF-α may not play an important role in stimulating sFlt-1 production in response to acute hypoxia, a more chronic hypoxia, or placental ischemia may be an important stimulus for enhanced sFlt-l production.

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