Uncoupled Endothelial Nitric Oxide Synthase and Oxidative Stress in a Rat Model of Pregnancy-Induced Hypertension

Mitchell, Brett M.; Cook, Leslie G.; Danchuk, Svitlana; Puschett, Jules B.

doi:10.1016/j.amjhyper.2007.08.007

Cited by 63 publications

(59 citation statements)

References 31 publications

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“…Clinically, recombinant IL-10 has been used with moderate success for the treatment of psoriasis and rheumatoid arthritis (3, 18), both immunological diseases characterized by an increased Th1-mediated inflammatory state. Whether or not IL-10 can ameliorate the hypertension, endothelial dysfunction, and proteinuria seen in PE remains unknown.We (15,22,34,35) have reported previously an experimental model of PE in which pregnant rats treated with low concentrations of DOCA and 0.9% saline exhibit hypertension, proteinuria, endothelial dysfunction, and IUGR, whereas nonpregnant rats receiving identical treatment do not. These DOCA/saline-treated rats have increased vascular oxidative stress due to uncoupled nitric oxide synthesis and elevated Address for reprint requests and other correspondence: B. M.…”

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confidence: 99%

“…These DOCA/saline-treated rats have increased vascular oxidative stress due to uncoupled nitric oxide synthesis and elevated levels of the proinflammatory cytokines/chemokines IL-2, IL-12, IFN␥, and RANTES (22,34). Furthermore, we (34) reported that excessive maternal immune responses play a major role in the development of PE-like symptoms in these rats as immunosuppression with either azathioprine or mycophenolate mofetil normalized systolic blood pressure, endothelial function, urinary protein excretion, and cytokine profiles.…”

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

Tinsley

South

Chiasson

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

100

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Tinsley JH, South S, Chiasson VL, Mitchell BM. Interleukin-10 reduces inflammation, endothelial dysfunction, and blood pressure in hypertensive pregnant rats. Am J Physiol Regul Integr Comp Physiol 298: R713-R719, 2010. First published January 6, 2010 doi:10.1152/ajpregu.00712.2009.-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 IFN␥ 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 IFN␥, 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. preeclampsia; anti-inflammatory; hypertension; endothelin-1 PREECLAMPSIA (PE), DIAGNOSED as de novo hypertension and proteinuria during pregnancy, and other hypertensive disorders of pregnancy affect ϳ10% of pregnancies in the US and are responsible for 15-20% of maternal deaths worldwide (8). PE is associated with decreased fetal development and increased risk of future maternal heart disease. Although recent scientific findings have greatly aided in explaining the potential mechanisms involved in the development of PE, the exact causes remain unknown and effective treatments for PE remain elusive.Abnormal maternal immune system responses play a key role in the development of PE (10,13,31). A current theory is that women who develop PE have abnormal immunological responses to the fetus and placenta and that the hypertension and proteinuria represent clinical signs of a mild form of fetal rejection, while severe forms of PE result in spontaneous abortion and fetal demise. Consistent with this abnormal immunological response, cli...

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confidence: 99%

mentioning

confidence: 99%

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

Tinsley

South

Chiasson

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

100

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“…• О 2 -неспряженою eNOS [11][12][13][14][15], а не лише, як раніше вважалося, його надходженням з таких джерел, як мітохондрії [16] , НАДФН-оксидаза [17][18][19], ксантиноксидаза [20] чи ліпо-та циклооксигенази [21].…”

Section: вступunclassified

“…Він може утворюватися за допомогою de novo синтезу індуцибельною NO-синтазою (іNOS), внас-лідок реутилізації стабільних метаболітів NO нітрат-і нітрит-аніонів відповідними редуктазами чи декомпозиції нітрозотіолів, що є депо NO, в судинній стінці [7][8][9][10]. Серед механізмів виникнення оксидативного стресу крім зниження активності ферментів антиоксидантної системи та сполук, що ней-тралізують вільні радикали, перевага остан-нім часом надається збільшенню генерації• О 2 -неспряженою eNOS [11][12][13][14][15] …”

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Nos Uncoupling Is Accompanied With Induction of the Oxidative Stress and the Cardiohemodynamics Disturbances in Hypertension

Kotsuruba¹,

Dorofeyeva²,

Сагач³

2015

Fiziol Zh

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Порівняли показники кардіогемодинаміки й оксидативного та нітрозативного стресу в серці й аорті у щурів лінії Вістар і у щурів зі спонтанною гіпертензією. На основі експериментально визначених показників розрахували індекс спряження конститутивних NO-синтаз (сNOS) ВСТУПНезважаючи на багаторічні інтен сив ні дос-лід жен ня, артеріальна гіпертен зія та її уск-ладнення залишаються се ред голов них при чин смертності в усьому світі. Ос тан-німи роками з'явилося достатньо фак тів, що свідчать про центральну роль у роз-вит ку артеріальної гіпертензії як окси-да тивного, так і нітрозативного стресу [1][2][3][4]. Останній викликається значним одно-часним підвищенням продукції нетоксичних супероксидного радикала ( • О 2 -) і оксиду азоту (NO), кожний з яких зумовлює утворення токсичних гідроксильного аніон-радикала ( • ОН) і пероксинітриту (ONOO -), та суттєвим зменшенням утворення NO ендотеліальною NO-синтазою (eNOS) [5,6]. Саме синтезова-ний цим ізоферментом NO є основним регуля тором тонусу та інших процесів у су-дин ній стінці. Крім регуляторного, в серці й аорті може утворюватися надлишковий NO, який викликає нітрозативний стрес. Він може утворюватися за допомогою de novo синтезу індуцибельною NO-синтазою (іNOS), внас-лідок реутилізації стабільних метаболітів NO нітрат-і нітрит-аніонів відповідними редуктазами чи декомпозиції нітрозотіолів, що є депо NO, в судинній стінці [7][8][9][10]. Серед механізмів виникнення оксидативного стресу крім зниження активності ферментів антиоксидантної системи та сполук, що ней-тралізують вільні радикали, перевага остан-нім часом надається збільшенню генерації• О 2 -неспряженою eNOS [11][12][13][14][15]

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“…Additionally, MBG inhibits the proliferation and migration of both cytotrophoblast and CHO cells [21] further interfering with the maturation process ( Figure 6). Finally, rats in which PE had been produced by the administration of DOCA and the replacement of tap water with saline as drinking water, demonstrated increased superoxide production by NADPH oxidase, superoxide degradation of BH4 and uncoupled eNOS which contributed to endothelial dysfunction [22].…”

Section: Other Hypertensive Statesmentioning

confidence: 99%

Involvement of the Bufodienolides in the Pathogenesis and Potential Therapy of Preeclampsia, the Acute Respiratory Distress Syndrome and Traumatic Brain Injury

Chen¹,

Abbas²,

Raju³

et al. 2017

Gynecol Obstet

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The purpose of this review is to provide detailed information on the evidence for marinobufagenin (MBG) as a predictive and causative factor in preeclampsia(PE), the acute respiratory distress syndrome(ARDS) and traumatic brain injury(TBI).In addition, evidence is provided that resibufogenin (RBG),the antagonist of MBG is effective in the treatment of all three diseases .Results from experiments conducted on animal models and in human subjects indicate that patients with PE, ARDS and TBI have increased urinary and serum MBG levels. In PE patients, MBG is elevated in the early stages of pregnancy. In ARDS, MBG was elevated in serum samples of hyperoxic rats. MBG levels were also elevated in concussed athletes and in rat studies in which TBI was induced. In the animal models, all three disease processes were prevented/treated by the administration of RBG. Human trials of MBG as a predictor of PE, ARDS and TBI are underway as are studies of RBG as a therapy with respect to its usefulness and safety. Early detection of PE will significantly reduce its effects on pregnancy. ARDS, which has a high mortality rate, would benefit from studies on employing RBG. TBI patients can be diagnosed much more quickly than currently possible utilizing MBG as an early indicator. Furthermore, RBG may serve as a therapy.

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Uncoupled Endothelial Nitric Oxide Synthase and Oxidative Stress in a Rat Model of Pregnancy-Induced Hypertension

Abstract: These data suggest that increased superoxide production by NADPH oxidase, peroxynitrite degradation of BH4, and uncoupled eNOS contribute to endothelial dysfunction in a rat model of pregnancy-induced hypertension.

Cited by 63 publications

References 31 publications

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

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

Nos Uncoupling Is Accompanied With Induction of the Oxidative Stress and the Cardiohemodynamics Disturbances in Hypertension

Involvement of the Bufodienolides in the Pathogenesis and Potential Therapy of Preeclampsia, the Acute Respiratory Distress Syndrome and Traumatic Brain Injury

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