Reduced Uterine Perfusion Pressure During Pregnancy in the Rat Is Associated With Increases in Arterial Pressure and Changes in Renal Nitric Oxide

Alexander, Barbara T.; Kassab, Salah; Miller, M. Todd; Abram, Sean R.; Reckelhoff, Jane F.; Bennett, William A.; Granger, Joey P.

doi:10.1161/01.hyp.37.4.1191

Cited by 243 publications

(309 citation statements)

References 21 publications

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“…* P Ͻ 0.05, measurements in tumor necrosis-␣ (TNF-␣; 1,000 pg/ml)-treated vessels are significantly different from corresponding measurements in control TNF-␣ nontreated vessels of virgin and pregnant rats; † P Ͻ 0.05, significantly different from corresponding measurements in endothelium-intact (ϩ Endo) vascular strips. L-NAME, N G -nitro-Larginine methyl ester; ODQ, 1H-[1,2,4]oxadiazolo [4,3]-quinoxalin-1-one. Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Increasing concentrations of ACh, bradykinin, or sodium nitroprusside were added, and the extent of vascular relaxation was measured. In other experiments, nontreated and TNF-␣-treated vascular strips were incubated for 30 min in the presence or the absence of N G -nitro-L-arginine methyl ester (L-NAME, 100 M), to inhibit NOS, or with 1H- [1,2,4]oxadiazolo [4,3]-quinoxalin-1-one (ODQ, 1 M), to inhibit cGMP production in smooth muscle (32,52), and the effects on the Phe-induced contraction and the ACh-induced relaxation of Phe contraction were measured. The concentrations of L-NAME and ODQ were selected based on previous studies, which have shown that these inhibitors are effective and specific at the concentrations used in this preparation (26,52,58,64).…”

Section: Animalsmentioning

confidence: 99%

“…The developed force was corrected for the cross-sectional area of each individual strip and was expressed as active stress (N/m 2 ) using the equation stress ϭ force/cross-sectional area, where cross-sectional area ϭ wet weight/(tissue density ϫ length of strip), and tissue density ϭ 1.055 g/cm 3 as previously described (35,59). Data from vascular strips of the same animal were averaged and presented as data from one animal, and n represented the number of animals.…”

Section: Animalsmentioning

confidence: 99%

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TNF-α enhances contraction and inhibits endothelial NO-cGMP relaxation in systemic vessels of pregnant rats

Giardina

Green

Cockrell

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

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. TNF-␣ enhances contraction and inhibits endothelial NO-cGMP relaxation in systemic vessels of pregnant rats. Am J Physiol Regulatory Integrative Comp Physiol 283: R130-R143, 2002. First published February 28, 2002 10.1152/ajpregu.00704. 2001.-Tumor necrosis factor-␣ (TNF-␣) is elevated in the plasma of preeclamptic women and may have a role in pregnancy-induced hypertension. However, whether the hemodynamic effects of TNF-␣ reflect the direct effects on vascular reactivity is unclear. We tested the hypothesis that TNF-␣ impairs endothelium-dependent relaxation and enhances vascular contraction in systemic vessels of pregnant rats. We measured isometric contraction in aortic strips isolated from virgin and pregnant Sprague-Dawley rats (nontreated vs. treated for 2 h with 10-1,000 pg/ml TNF-␣). In endotheliumintact vascular strips, TNF-␣ caused greater enhancement of phenylephrine (Phe) contraction in pregnant than virgin rats. TNF-␣ caused significant inhibition of ACh-and bradykinin-induced vascular relaxation and nitrite/nitrate production that were more prominent in pregnant than virgin rats. N G -nitro-L-arginine methyl ester [L-NAME, 100 M, an inhibitor of nitric oxide (NO) synthase] or 1H-[1,2,4]oxadiazolo[4,3]-quinoxalin-1-one (ODQ, 1 M, an inhibitor of cGMP production in smooth muscle) inhibited ACh relaxation and enhanced Phe contraction in nontreated but to a lesser extent in TNF-␣-treated vessels, particularly those of pregnant rats. Endothelium removal enhanced Phe contraction in nontreated but not TNF-␣-treated vessels, especially those of pregnant rats. Relaxation of Phe contraction with the NO donor sodium nitroprusside was not different between nontreated and TNF-␣-treated vessels. Thus TNF-␣ enhances vascular contraction and inhibits endothelium-dependent NO-cGMP-mediated vascular relaxation in systemic vessels, particularly those of pregnant rats. The results support a direct role for TNF-␣ as a possible mediator of increased vascular resistance associated with pregnancy-induced hypertension.cytokines; endothelium; nitric oxide; pregnancy; arterial pressure; tumor necrosis factor-␣ NORMAL PREGNANCY IS OFTEN associated with decreased systemic vascular resistance and arterial pressure and reduced vascular reactivity to circulating vasoconstrictors (20,35,46,51). The hemodynamic and vascular changes associated with normal pregnancy have been attributed in part to increased nitric oxide (NO) synthesis by various cells including the vascular endothelial cells (1,18,54,62,69). This is supported by studies showing that the tissue expression and activity of NO synthase (NOS) are enhanced during late gestation (4,13,61,68) and that the metabolic production and plasma level of guanosine 3Ј,5Ј-cyclic monophosphate (cGMP), a second messenger of NO and a cellular mediator of vascular smooth muscle relaxation (30,34), are increased during pregnancy (15).In 5-10% of pregnancies, women develop a condition called preeclampsia, which is characterized by proteinuria, increased intravascular coagulation and sy...

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Section: Resultsmentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

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TNF-α enhances contraction and inhibits endothelial NO-cGMP relaxation in systemic vessels of pregnant rats

Giardina

Green

Cockrell

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

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“…[17][18][19][20][21] Experimental studies in animal models have suggested that a reduction in the uteroplacental perfusion pressure and the ensuing placental ischemia/hypoxia during late pregnancy initiate a cascade of hemodynamic and vascular changes that lead to increased systemic vascular resistance and hypertension. [17][18][19][20][21] For example, studies from our laboratory and others' have demonstrated that reduction in uteroplacental perfusion in pregnant rats results in significant hemodynamic changes and a hypertensive state that closely resembles hypertension of pregnancy in women. 18,20,21 We have also found that the reduction in uteroplacental perfusion pressure in pregnant rats is associated with decreased vascular relaxation and enhanced vascular contraction, suggesting that these vascular changes could contribute to the increased vascular resistance and hypertension of pregnancy.…”

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confidence: 99%

Reduced Endothelial NO-cGMP–Mediated Vascular Relaxation and Hypertension in IL-6–Infused Pregnant Rats

Orshal

Khalil

2004

Hypertension

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Abstract-Placental ischemia during pregnancy is associated with increased plasma cytokines such as interleukin-6 (IL-6), which may contribute to increased vascular resistance and hypertension of pregnancy. We tested the hypothesis that an increase in plasma IL-6 during pregnancy is associated with impaired endothelium-dependent relaxation, enhanced vascular contraction, and hypertension. Systolic blood pressure was measured in virgin and pregnant Sprague-Dawley rats non-treated or infused with IL-6 (200 ng/kg per day for 5 days). Isometric contraction was measured in isolated aortic strips, and endothelial nitric oxide (NO) synthase (eNOS) was measured in aortic homogenate using Western blots. Blood pressure was greater in IL-6 -infused (146Ϯ3) than in control pregnant rats (117Ϯ2 mm Hg). In endothelium-intact vascular strips, phenylephrine (Phe) caused greater increase in active stress in IL-6 -infused (maximum: 10.6Ϯ0.6) than in control pregnant rats (maximum: 4.1Ϯ0.3ϫ10 4 N/m 2 ). Acetylcholine (ACh)-induced relaxation of Phe contraction and vascular eNOS protein and nitrite/nitrate production were less in IL-6 -infused than in control pregnant rats.Ϫ5 mol/L), inhibitor of cGMP production in smooth muscle, inhibited ACh-induced relaxation and enhanced Phe-induced stress in control but not IL-6 -infused pregnant rats. Endothelium removal enhanced Phe-induced stress in control but not in IL-6 -infused pregnant rats. The blood pressure and vascular Phe-induced contraction, ACh relaxation, and eNOS protein were not different between control and IL-6 -infused virgin rats. Thus, an endotheliumdependent NO-cGMP-mediated relaxation pathway is inhibited in systemic vessels of pregnant rats infused with IL-6. The results support a role for IL-6 as a possible mediator of the increased vascular resistance during hypertension of pregnancy. Key Words: blood pressure Ⅲ endothelium Ⅲ nitric oxide Ⅲ pregnancy N ormal pregnancy is associated with reduced systemic vascular resistance and arterial pressure and decreased vascular contraction to vasoconstrictor agonists. 1-3 The hemodynamic and vascular changes observed during normal pregnancy have been attributed, in part, to increased nitric oxide (NO) production by various cells, including vascular endothelial cells. 4 -8 This is supported by reports that the tissue expression and activity of NO synthase are increased during late gestation 9 -11 and that the metabolic production and plasma level of cyclic guanosine 3Ј,5Ј-monophosphate (cGMP), a second messenger of NO and a cellular mediator of vascular smooth muscle relaxation, 12 are increased during pregnancy. 13 In 3% to 5% of pregnancies, a condition called preeclampsia develops, which is characterized by increased intravascular coagulation, proteinuria, increased systemic vascular resistance ,and hypertension. 14 -16 Although preeclampsia is a major cause of maternal and fetal morbidity and mortality, the mechanisms of this disorder have not yet been clearly identified. Because of the difficulty of performing mechanistic...

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“…A thin endometrial lining may mirror previous or a current uterine pathology, and with the importance that uterine artery blood flow has on endometrial growth, we could conclude that improving uterine blood flow may facilitate achieving higher pregnancy rates. The significance of nitric oxide (NO) as a modulator of uterine blood flow through the relaxation of vascular smooth muscle by a cyclic guanosine monophosphate (cGMP)-mediated pathway has been studied [8]. Phosphodiesterase (PDE) enzymes also play a role in the NO-CGMP cycle by hydrolyzing cGMP through degrading the phosphodiester bond in these second messenger molecules and so regulating the signal transduction mediated by cGMP.…”

Section: Introductionmentioning

confidence: 99%

Effect of Vaginal Sildenafil on in Vitro Fertilization Success Rates in Women With Previous Failed in Vitro Fertilization Attempts

Tehraninejad

Khazei

Ayati

et al. 2018

Asian J Pharm Clin Res

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Objectives: Endometrial thickness of <9 mm is a predictor of in vitro fertilization (IVF) failure, although neither pregnancy rates nor the pregnancy outcomes are dependent on the endometrial thickness alone. The impact that uterine artery blood flow has on endometrial growth is dependent on nitric oxide which concentrations could be altered by halting a cyclic guanosine monophosphate-mediated pathway with a phosphodiesterase type 5 selective inhibitor such as sildenafil. Methods:In this clinical trial, 72 patients aged below 45 years which have had at least two earlier failed IVF attempts were randomly split into two groups each consisting of 36 patients. Both groups were started on a long IVF protocol. The case group was also administered 100 mg vaginal sildenafil suppositories daily, starting on day 3 of menstruation which was continued until human chorionic gonadotropin administration. Endometrial thickness was measured using ultrasonography in both groups plus pregnancy rates were assessed in both groups.

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Reduced Uterine Perfusion Pressure During Pregnancy in the Rat Is Associated With Increases in Arterial Pressure and Changes in Renal Nitric Oxide

Cited by 243 publications

References 21 publications

TNF-α enhances contraction and inhibits endothelial NO-cGMP relaxation in systemic vessels of pregnant rats

TNF-α enhances contraction and inhibits endothelial NO-cGMP relaxation in systemic vessels of pregnant rats

Reduced Endothelial NO-cGMP–Mediated Vascular Relaxation and Hypertension in IL-6–Infused Pregnant Rats

Effect of Vaginal Sildenafil on in Vitro Fertilization Success Rates in Women With Previous Failed in Vitro Fertilization Attempts

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