Adaptive changes of mesenteric arteries in pregnancy: a meta-analysis

2012 ◽  
Vol 303 (6) ◽  
pp. H639-H657 ◽  
Author(s):  
Joris van Drongelen ◽  
Carlijn R. Hooijmans ◽  
Frederik K. Lotgering ◽  
Paul Smits ◽  
Marc E. A. Spaanderman
Keyword(s):  
Arterial Compliance ◽  
Meta Analysis ◽  
Late Pregnancy ◽  
Normal Pregnancy ◽  
Late Gestation ◽  
Mesenteric Arteries ◽  
Sprague Dawley ◽  
Receptor Level ◽  
Sprague Dawley Rats ◽  
Flow Mediated Vasodilation

The vascular response to pregnancy has been frequently studied in mesenteric artery models by investigating endothelial cell (EC)- and smooth muscle cell (SMC)-dependent responses to mechanical (flow-mediated vasodilation, myogenic reactivity, and vascular compliance) and pharmacological stimuli (G protein-coupled receptor responses: GqEC, GsSMC, GqSMC). It is unclear to what extent these pathways contribute to normal pregnancy-induced vasodilation across species, strains, and/or gestational age and at which receptor level pregnancy affects the pathways. We performed a meta-analysis on responses to mechanical and pharmacological stimuli associated with pregnancy-induced vasodilation of mesenteric arteries and included 55 (188 responses) out of 398 studies. Most included studies (84%) were performed in Wistar and Sprague-Dawley rats (SDRs) and compared late gestation versus nonpregnant controls (80%). Pregnancy promotes flow-mediated vasodilation in all investigated species. Only in SDRs, pregnancy additionally stimulates both vasodilator GqEC sensitivity (EC50 reduced by −0.76 [−0.92, −0.60] log[M]) and GsSMC sensitivity (EC50 reduced by −0.51 [−0.82, −0.20] log[M]), depresses vasopressor GqSMC sensitivity (EC50 increase in SDRs by 0.23 [0.16, 0.31] log[M]), and enhances arterial compliance. We conclude that 1) pregnancy facilitates flow-mediated vasodilation at term among all investigated species, and the contribution of additional vascular responses is species and strain specific, and 2) late pregnancy mediates vasodilation through changes at the receptor level for the substances tested. The initial steps of vasodilation in early pregnancy remain to be elucidated.

Abstract 206: Hyperleptinemia Increases Blood Pressure and Decreases Pup Weight in Pregnant Rats

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Ana C Palei ◽  
Eric M George ◽  
Marietta Arany ◽  
Kathy Cockrell ◽  
Joey P Granger
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Normal Pregnancy ◽  
Developed Countries ◽  
Late Gestation ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Glucose Levels ◽  
Sprague Dawley Rats ◽  
Relationship Of

While the relationship of obesity to cardiovascular disease is well recognized, it also has important implications for pregnancy outcomes. Indeed, there is compelling evidence that obesity increases the risk of preeclampsia (PE). The risk of severe and mild PE and PE occurring in early and late gestation are greater in obese and overweight women. Despite the fact that obesity is the leading attributable risk for PE in developed countries, the pathophysiological mechanisms whereby obesity and metabolic factors such as leptin increases the risk for developing PE are unclear. Hyperleptinemia over the levels seen in normal pregnancy has been associated with preeclampsia. Thus the aim of this study was to investigate whether chronic hyperleptinemia causes changes in cardiovascular, metabolic and reproductive systems of pregnant rats. On gestational day (GD) 14, Sprague Dawley rats were assigned to normal pregnant (NP, n=8) group or to NP plus Leptin group (NP+Lep, n=8), in which miniosmotic pump with leptin (0.5 μg/kg/min) was placed intraperitoneally. On GD 19, mean arterial pressure (MAP) was recorded, rats were sacrificed, and blood, placentas and pups were collected. Body weight (BW) and food intake (FI) were measured on GD 16-18. Serum leptin concentration was elevated in NP+Lep compared with NP (0.82 ± 0.05 vs 17.98 ± 2.75 ng/mL, P<0.05). Circulating insulin and glucose levels were similar in NP and NP+Lep groups (both P>0.05). MAP was higher in NP+Lep compared with NP (102.40 ± 2.38 vs 121.30 ± 8.13 mmHg, P<0.05). BW was decreased in NP+Lep compared with NP at GD 19 (330.90 ± 9.08 vs 284.10 ± 8.58 g, P<0.05), probably due to the reduced FI of the NP+Ins group compared with NP during GD 16-18 (23.45 ± 0.61 vs 8.61 ± 0.83 g/day, P<0.05). Although the number of viable fetuses per rat was similar between groups (P>0.05), fetuses and placentas of the NP+Lep group were lighter than those of the NP group (2.29 ± 0.06 vs 2.11 ± 0.06 g and 0.58 ± 0.01 vs 0.50 ± 0.02 g, respectively, both P<0.05). In conclusion, leptin increases blood pressure, despite its effect of reducing body weight during pregnancy, representing a possible mechanism to induce hypertension in preeclampsia. In addition, leptin decreases pup and placental weights, which could lead to abnormal fetal outcomes.

ACE2 and ANG-(1-7) in the rat uterus during early and late gestation

2008 ◽  
Vol 294 (1) ◽  
pp. R151-R161 ◽  
Author(s):  
Liomar A. A. Neves ◽  
Kathryn Stovall ◽  
JaNae Joyner ◽  
Gloria Valdés ◽  
Patricia E. Gallagher ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
Perfusion Pressure ◽  
Late Pregnancy ◽  
Late Gestation ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Induced Hypertension ◽  
Uteroplacental Blood Flow ◽  
Uterine Perfusion

The present study was designed to determine ANG peptide content [ANG I, ANG II, ANG-(1-7)], ACE2 mRNA, and the immunocytochemical distribution of ANG-(1-7) and ACE2 in the uteroembryonic unit during early and late gestation in Sprague-Dawley rats and in a rat model of pregnancy-induced hypertension, the reduced uterine perfusion pressure (RUPP) model. At early pregnancy ANG-(1-7) and ACE2 staining were localized in the primary and secondary decidual zone and luminal and glandular epithelial cells. During late gestation, ANG-(1-7) and ACE2 staining was visualized in the labyrinth placenta and amniotic and yolk sac epithelium. Uterine ANG II concentration at early pregnancy was significantly decreased by 21–55% in the implantation and interimplantation sites compared with virgin rats, whereas ANG-(1-7) levels were maintained at prepregnancy levels. At late gestation, uterine concentrations of ANG I and ANG II were significantly increased (30% and 25%, respectively). In RUPP animals, ANG-(1-7) concentration is significantly reduced in the uterus (181 ± 16 vs. 372 ± 74 fmol/g of tissue) and placenta (143 ± 26 vs. 197 ± 20 fmol/g of tissue). ACE2 mRNA increased in the uterus of early pregnant compared with virgin rats, yet within the implantation site it was downregulated. At late pregnancy, ACE2 mRNA is elevated by 58% in the uterus and decreased by 59% in RUPP animals. The regulation of ANG-(1-7) and ACE2 in early and late pregnancy supports the hypothesis that ANG-(1-7) and ACE2 may act as a local autocrine/paracrine regulator throughout pregnancy, participating in the early (angiogenesis, apoptosis, and growth) and late (uteroplacental blood flow) events of pregnancy.

Abstract 637: Hydrogen Sulfide Acts on Endothelial Cells to Elicit Dilation.

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Nancy L Kanagy ◽  
Jessica M Osmond ◽  
Olan Jackson-Weaver ◽  
Benjimen R Walker
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Hydrogen Sulfide ◽  
Mesenteric Arteries ◽  
Direct Effects ◽  
Sprague Dawley ◽  
Imaging Studies ◽  
Knock Out ◽  
Event Frequency ◽  
Sprague Dawley Rats

Hydrogen sulfide (H 2 S), produced by the enzyme cystathionine-γ lyase (CSE), dilates arteries by hyperpolarizing and relaxing vascular smooth muscle cells (VSMC) and CSE knock-out causes hypertension and endothelial dysfunction showing the importance of this system. However, it is not clear if H 2 S-induced VSMC depolarization and relaxation is mediated by direct effects on VSMC or indirectly through actions on endothelial cells (EC). We reported previously that disrupting EC prevents H 2 S-induced vasodilation suggesting H 2 S might act directly on EC. Because inhibiting large-conductance Ca 2+ -activated K + (BK Ca ) channels also inhibits H 2 S-induced dilation, we hypothesized that H 2 S activates EC BK Ca channels to hyperpolarize EC and increase EC Ca 2+ which stimulates release of a secondary hyperpolarizing factor. Small mesenteric arteries from male Sprague-Dawley rats were used for all experiments. We found that EC disruption prevented H 2 S-induced VSMC membrane potential ( E m ) hyperpolarization. Blocking EC BK Ca channels with luminal application of the BK Ca inhibitor, iberiotoxin (IbTx, 100 nM), also prevented NaHS-induced dilation and VSMC hyperpolarization but did not affect resting VSMC E m showing EC specific actions. Sharp electrode recordings in arteries cut open to expose EC demonstrated H 2 S-induced hyperpolarization of EC while Ca 2+ imaging studies in fluor-4 loaded EC showed that H 2 S increases EC Ca 2+ event frequency. Thus H 2 S can act directly on EC. Inhibiting the EC enzyme cytochrome P 450 2C (Cyp2C) with sulfaphenazole also prevented VSMC depolarization and vasodilation. Finally, inhibiting TRPV4 channels to block the target of the Cyp2C product 11,12-EET inhibited NaHS-induced dilation. Combined with our previous report that CSE inhibition decreases BK Ca currents in EC, these results suggest that H 2 S stimulates EC BK Ca channels and activates Cyp2C upstream of VSMC hyperpolarization and vasodilation.

Renal interstitial hydrostatic pressure and pressure natriuresis in pregnant rats

2000 ◽  
Vol 279 (2) ◽  
pp. F353-F357 ◽  
Author(s):  
Ali A. Khraibi
Keyword(s):  
Hydrostatic Pressure ◽  
Perfusion Pressure ◽  
Fractional Excretion ◽  
Normal Pregnancy ◽  
Renal Perfusion ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Sprague Dawley Rats ◽  
Fractional Excretion Of Sodium ◽  
Pressure Natriuresis

The objective of this study was to test the hypothesis that a decrease in renal interstitial hydrostatic pressure (RIHP) accounts for the blunted pressure natriuresis during pregnancy. RIHP was measured in nonpregnant (NP; n = 9), midterm pregnant (MP; 12–14 days after conception; n = 10), and late-term pregnant (LP; 18–21 days after conception; n = 12) female Sprague-Dawley rats at two renal perfusion pressure (RPP) levels (99 and 120 mmHg). At the lower RPP level, RIHP was 5.9 ± 0.3 mmHg for NP, 3.4 ± 0.4 mmHg for MP ( P < 0.05 vs. NP), and 2.9 ± 0.1 mmHg for LP ( P < 0.05 vs. NP) rats. The increase in RPP from 99 to 120 mmHg resulted in pressure natriuretic and diuretic responses in all groups; however, the increases in fractional excretion of sodium (ΔFENa), urine flow rate (ΔV), and ΔRIHP were significantly greater ( P < 0.05) in NP compared with both MP and LP rats. ΔFENa, ΔV, and ΔRIHP were 2.06 ± 0.28%, 81.44 ± 14.10 μl/min, and 3.0 ± 0.5 mmHg for NP; 0.67 ± 0.13%, 28.03 ± 5.28 μl/min, and 0.5 ± 0.2 mmHg for MP; and 0.48 ± 0.12%, 18.14 ± 4.70 μl/min, and 0.4 ± 0.1 mmHg for LP rats. In conclusion, RIHP is significantly lower in pregnant compared with nonpregnant rats at similar RPP levels. Also, the ability of pregnant rats to increase RIHP in response to an increase in RPP is blunted. These changes in RIHP may play an important role in the blunted pressure natriuresis and contribute to the conservation of sodium and water that is critical for fetal growth and development during normal pregnancy.

scholarly journals Relaxin Is Essential for Systemic Vasodilation and Increased Global Arterial Compliance during Early Pregnancy in Conscious Rats

Endocrinology ◽  
2006 ◽  
Vol 147 (11) ◽  
pp. 5126-5131 ◽  
Author(s):  
Dan O. Debrah ◽  
Jackie Novak ◽  
Julianna E. Matthews ◽  
Rolando J. Ramirez ◽  
Sanjeev G. Shroff ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Early Pregnancy ◽  
Neutralizing Antibodies ◽  
Arterial Compliance ◽  
Normal Pregnancy ◽  
Systemic Circulation ◽  
Mesenteric Arteries ◽  
Systemic Hemodynamics ◽  
Female Rats ◽  
Pregnant Rats

During early pregnancy, there are marked increases in cardiac output (CO) and global arterial compliance (AC), as well as decreases in systemic vascular resistance (SVR). We recently reported that administration of recombinant human relaxin to nonpregnant female rats elicits changes in systemic hemodynamics and arterial mechanical properties similar to those observed during normal pregnancy. In the present study, we directly tested whether endogenous relaxin mediates the cardiovascular adaptations of pregnancy by neutralizing circulating relaxin with monoclonal antibodies during early gestation. Relaxin neutralizing antibodies were administered daily, beginning on d 8 of rat gestation, to block the functional effects of circulating relaxin. Systemic hemodynamics and arterial properties were assessed between gestational d 11 and 15 using techniques we have previously reported. Pregnant rats administered the neutralizing antibodies failed to exhibit the gestational increases in stroke volume, CO, and global AC or decreases in SVR that were observed in control pregnant rats administered an irrelevant antibody against fluorescein or PBS. In fact, in the pregnant rats administered the relaxin neutralizing antibodies, cardiovascular parameters were not statistically different from those in virgin rats. Interestingly, small renal and first-order mesenteric arteries isolated from midterm pregnant rats administered either relaxin-neutralizing or control antibodies did not exhibit any changes in passive mechanical properties compared with virgin rats. These findings indicate that circulating relaxin mediates the transition of the systemic circulation from the virgin to the pregnant state in the gravid rat model, suggesting a potential role for aberrant relaxin regulation in abnormal pregnancies wherein these cardiovascular adaptations are inadequate or excessive.

scholarly journals Endothelium-Independent Relaxation of Vascular Smooth Muscle Induced by Persimmon-Derived Polyphenol Phytocomplex in Rats

Nutrients ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 89
Author(s):  
Risa Kudo ◽  
Katsuya Yuui ◽  
Shogo Kasuda
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Mesenteric Arteries ◽  
Inositol Triphosphate ◽  
Sprague Dawley ◽  
Vasorelaxant Effect ◽  
Sprague Dawley Rats ◽  
The Mean ◽  
Artery Disease ◽  
Nitric Oxide Pathway

The vasorelaxant effect of polyphenols is well known, and the mortality rate due to coronary artery disease is low in people who consume polyphenol-containing foods. We aimed to elucidate the mechanism by which polyphenols derived from persimmon juice (PJ) and persimmon leaves (PLs) induce vasorelaxation and suppress vasocontraction in the superior mesenteric arteries isolated from male Sprague Dawley rats. Vasocontraction was induced with 1 µM phenylephrine, and polyphenol-induced vasorelaxation was expressed as a percentage of the previous tone induced by phenylephrine. PJ powder (100 mg/L) induced higher levels of vasorelaxation (mean ± standard error of the mean, 88.6% ± 4.4%) than PLs powder (1 g/L; 72.0% ± 10.8%). Nitric oxide pathway inhibitors (NG-nitro-L-arginine methyl ester + carboxy-PTIO) did not affect persimmon-derived polyphenol-induced vasorelaxation, whereas potassium chloride, tetraethylammonium, and potassium-channel inhibitors did. Vasorelaxation was endothelium independent with both extracts. Phenylephrine-induced vasocontraction was suppressed by pretreatment with PJ and PLs powder, even when inositol triphosphate-mediated Ca2+ release and extracellular Ca2+ influx were inhibited. These results suggest that persimmon-derived polyphenol phytocomplex cause vasorelaxation and inhibit vasocontraction through hyperpolarization of smooth muscle cells. Persimmon-derived polyphenols may be able to prevent cardiovascular diseases caused by abnormal contraction of blood vessels.

scholarly journals Early Gestational Exposure to Inhaled Ozone Impairs Maternal Uterine Artery and Cardiac Function

2020 ◽  
Author(s):  
Marcus Garcia ◽  
Raul Salazar ◽  
Thomas Wilson ◽  
Selita Lucas ◽  
Guy Herbert ◽  
...  
Keyword(s):  
Uterine Artery ◽  
Gestational Hypertension ◽  
Resistance Index ◽  
Cardiovascular Effects ◽  
Late Gestation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Transcriptional Changes ◽  
Adverse Pregnancy ◽  
Underlying Mechanisms

Abstract Exposure to air pollutants such as ozone (O3) is associated with adverse pregnancy outcomes, including higher incidence of gestational hypertension, preeclampsia, and peripartum cardiomyopathy; however, the underlying mechanisms of this association remain unclear. We hypothesized that O3 exposures during early placental formation would lead to more adverse cardiovascular effects at term for exposed dams, as compared with late-term exposures. Pregnant Sprague Dawley rats were exposed (4 h) to either filtered air (FA) or O3 (0.3 or 1.0 ppm) at either gestational day (GD)10 or GD20, with longitudinal functional assessments and molecular endpoints conducted at term. Exposure at GD10 led to placental transcriptional changes at term that were consistent with markers in human preeclampsia, including reduced mmp10 and increased cd36, fzd1, and col1a1. O3 exposure, at both early and late gestation, induced a significant increase in maternal circulating soluble FMS-like tyrosine kinase-1 (sFlt-1), a known driver of preeclampsia. Otherwise, exposure to 0.3 ppm O3 at GD10 led to several late-stage cardiovascular outcomes in dams that were not evident in GD20-exposed dams, including elevated uterine artery resistance index and reduced cardiac output and stroke volume. GD10 O3 exposure proteomic profile in maternal hearts characterized by a reduction in proteins with essential roles in metabolism and mitochondrial function, whereas phosphoproteomic changes were consistent with pathways involved in cardiomyopathic responses. Thus, the developing placenta is an indirect target of inhaled O3 and systemic maternal cardiovascular abnormalities may be induced by O3 exposure at a specific window of gestation.

Effects of relaxin on systemic arterial hemodynamics and mechanical properties in conscious rats: sex dependency and dose response

2005 ◽  
Vol 98 (3) ◽  
pp. 1013-1020 ◽  
Author(s):  
Dan O. Debrah ◽  
Kirk P. Conrad ◽  
Lee A. Danielson ◽  
Sanjeev G. Shroff
Keyword(s):  
Dose Response ◽  
Arterial Compliance ◽  
Chronic Administration ◽  
Late Pregnancy ◽  
High Serum ◽  
Late Gestation ◽  
Female Rats ◽  
Male Rats ◽  
Serum Concentrations ◽  
Arterial Load

We previously showed that chronic administration of recombinant human relaxin (rhRLX; 4 μg/h) to conscious female, nonpregnant rats to reach serum levels corresponding to early to midgestation (∼20 ng/ml) increases cardiac output (CO) and global arterial compliance (AC) and decreases systemic vascular resistance (SVR), comparable to changes observed in midterm pregnancy. The goals of this study were to test whether chronic administration of rhRLX (4 μg/h) to conscious male rats will yield similar changes in CO and systemic arterial load and to determine whether higher infusion rates of rhRLX (50 μg/h) administered to nonpregnant female rats yielding serum concentrations corresponding to late pregnancy (∼80 ng/ml) will further modify CO and SVR and global AC comparable to late gestation. CO and systemic arterial load, as quantified by SVR and AC, were obtained by using the same methods as in our previous studies. With respect to baseline, chronic rhRLX administration to male rats over 10 days at 4 μg/h increased both CO (20.5 ± 4.2%) and AC (19.4 ± 6.9%) and reduced SVR (12.7 ± 3.9%). These results were comparable to those elicited by the hormone in nonpregnant female rats. In contrast, neither acute (over 4 h) nor chronic (over 6 days) infusion of the higher dose of rhRLX administered to conscious female rats resulted in significant changes in CO, AC, or SVR from baseline. We conclude that 1) rhRLX increases CO and AC and reduces SVR irrespective of sex, and 2) the rhRLX dose response is biphasic insofar as significant alterations in CO and systemic arterial load fail to occur at high serum concentrations.

Gasping and autoresuscitation in the developing rat: effect of antecedent intermittent hypoxia

2002 ◽  
Vol 92 (3) ◽  
pp. 1141-1144 ◽  
Author(s):  
David Gozal ◽  
Evelyne Gozal ◽  
Stephen R. Reeves ◽  
Andrew J. Lipton
Keyword(s):  
Sudden Infant Death Syndrome ◽  
Intermittent Hypoxia ◽  
Normal Pregnancy ◽  
Sudden Infant Death ◽  
Sudden Infant ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Developing Rat ◽  
Survival Mechanisms ◽  
Related Survival

Gasping is a critically important mechanism for autoresuscitation and survival during extreme tissue hypoxia. Evidence of antecedent hypoxia in sudden infant death syndrome suggests that intermittently occurring hypoxic episodes may modify gasping and autoresuscitation. To examine this issue, an intermittent hypoxia (IH) profile consisting of alternating room air and 10% O2-balance N2 every 90 s was applied to pregnant Sprague-Dawley rats (IHRA; n = 50) and to pups after a normal pregnancy (RAIH; n = 50) as well as to control pups (RARA; n = 50). At postnatal day 5, pups were exposed to 95% N2-5% CO2, and gasping and the ability to autoresuscitate were assessed. Compared with RARA, IHRA- and RAIH-exposed pups had a reduced number of gasps, decreased overall gasp duration, and were less likely to autoresuscitate on introduction of room air to the breathing mixture during the last phase of gasping ( P < 0.001 vs. RARA). We conclude that both prenatal and early postnatal IH adversely affect gasping and related survival mechanisms.

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