Role of Extracellular Calcium and Calcium Sensitization in the Anti-Contractile Effect of Perivascular Adipose Tissue in Pregnant Rat Aorta

Pharmacology ◽  
2019 ◽  
Vol 104 (5-6) ◽  
pp. 359-367 ◽  
Author(s):  
Aishah Al-Jarallah ◽  
Elsie Oommen ◽  
Lilly Chacko Verghese ◽  
Mabayoje A. Oriowo
Keyword(s):  
Adipose Tissue ◽  
Inhibitory Effect ◽  
Extracellular Calcium ◽  
Pregnant Rats ◽  
Perivascular Adipose Tissue ◽  
Pregnant Rat ◽  
Calcium Sensitization ◽  
Contractile Effect ◽  
Significant Difference ◽  
Gf 109203X

Previous studies have shown that the anti-contractile effect of the perivascular adipose tissue (PVAT) is attenuated in pregnancy. In the present investigation, we have examined the possibility that this loss of anti-contractile effect could be due to changes in calcium mobilization. PVAT exerted anti-contractile effect against 5-hydroxytryptamine (5-HT)-induced contractions of aorta segments from pregnant and non-pregnant rats and this anti-contractile effect was attenuated in segments from pregnant rats. Nifedipine (10–6 mol/L), an inhibitor of L-type dihydropyridine calcium channels, significantly reduced 5-HT-induced contraction of aorta segments from non-pregnant and pregnant rats with and without PVAT. The inhibitory effect of nifedipine against 5-HT-induced contractions was attenuated in PVAT-free aorta segments from pregnant rats. However, while PVAT reduced the effectiveness of nifedipine in aorta segments from non-pregnant rats, it partially restored the inhibitory effect of nifedipine in aorta segments from pregnant rats. Inhibitors of calcium sensitization, Y-27632 (10–6 mol/L) and GF 109203X (10–6 mol/L), significantly reduced 5-HT-induced contractions of PVAT-free aorta segments from non-pregnant and pregnant rats. Both inhibitors, however, were less effective in aorta segments from pregnant rats. The presence of PVAT reduced the effectiveness of Y-27632 and GF 109203X in aorta segments from pregnant and non-pregnant rats. Protein expression of Rho-associated protein kinase (ROCK) I and II was detected in aorta segments and PVAT from pregnant and non-pregnant rats. There was a reduction in the expression of both isoforms in aorta segments but not PVAT from pregnant rats. In addition, there was no significant difference in the expression of ROCK-I and ROCK-II in PVAT from pregnant and non-pregnant rats. We concluded that the loss of anti-contractile effect of PVAT in aorta segments from pregnant rats could be due to increased influx of extracellular calcium through nifedipine-sensitive dihydropyridine channels.

scholarly journals Restoring Perivascular Adipose Tissue Function in Obesity Using Exercise

2021 ◽  
Author(s):  
Sophie N Saxton ◽  
Lauren K Toms ◽  
Robert G Aldous ◽  
Sarah B Withers ◽  
Jacqueline Ohanian ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Contractile Function ◽  
Ex Vivo ◽  
Vascular Complications ◽  
Electrical Field Stimulation ◽  
Organic Cation Transporter ◽  
Nervous Stimulation ◽  
Perivascular Adipose Tissue ◽  
Contractile Effect ◽  
Organic Cation Transporter 3

AbstractPurposePerivascular adipose tissue (PVAT) exerts an anti-contractile effect which is vital in regulating vascular tone. This effect is mediated via sympathetic nervous stimulation of PVAT by a mechanism which involves noradrenaline uptake through organic cation transporter 3 (OCT3) and β3-adrenoceptor-mediated adiponectin release. In obesity, autonomic dysfunction occurs, which may result in a loss of PVAT function and subsequent vascular disease. Accordingly, we have investigated abnormalities in obese PVAT, and the potential for exercise in restoring function.MethodsVascular contractility to electrical field stimulation (EFS) was assessed ex vivo in the presence of pharmacological tools in ±PVAT vessels from obese and exercised obese mice. Immunohistochemistry was used to detect changes in expression of β3-adrenoceptors, OCT3 and tumour necrosis factor-α (TNFα) in PVAT.ResultsHigh fat feeding induced hypertension, hyperglycaemia, and hyperinsulinaemia, which was reversed using exercise, independent of weight loss. Obesity induced a loss of the PVAT anti-contractile effect, which could not be restored via β3-adrenoceptor activation. Moreover, adiponectin no longer exerts vasodilation. Additionally, exercise reversed PVAT dysfunction in obesity by reducing inflammation of PVAT and increasing β3-adrenoceptor and OCT3 expression, which were downregulated in obesity. Furthermore, the vasodilator effects of adiponectin were restored.ConclusionLoss of neutrally mediated PVAT anti-contractile function in obesity will contribute to the development of hypertension and type II diabetes. Exercise training will restore function and treat the vascular complications of obesity.

scholarly journals THE THE TERATOGENIC EFFECTS OF ETHANOLIC EXTRACT OF BINTANGUR LEAVES (CALOPHYLLUM SOULATTRI BURM. F) ON FEMALE WHITE RATS

2019 ◽  
pp. 160-163
Author(s):  
INARAH FAJRIATY ◽  
HAFRIZAL RIZA ◽  
FAJAR NUGRAHA ◽  
FRENGKI FRIANTO
Keyword(s):  
Body Weight ◽  
Comparison Group ◽  
Ethanol Extract ◽  
Teratogenic Effect ◽  
Control Group ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
White Rats ◽  
Significant Difference ◽  
Skeletal Formation

Objectives: Drugs can cause undesired effects on the fetus during pregnancy, especially embryonic/organogenesis which could lead to defects in the fetus because some types of drugs can penetrate the placenta and will undergo biotransformation into a highly reactive compound that has the potential to become a teratogenic compound. The aim of this research was to examine the teratogenic effect of bintangur leaves (Calophyllum soulattri Burm. F) ethanol extract to Sprague Dawley strain white rats. Methods: The white rats are divided into four treatment groups: Control group was given carboxymethyl cellulose Na 1%, comparison group was given trimethoprim 360 mg/kg BW, C. soulattri leaves ethanol extract (CLE) 100 mg/kg BW, and CLE 500 mg/kg BW. The treatment was administrated since organogenesis period. Cesarian section was performed to pregnant rat at the 20th day to separate the fetuses. Observation covered body weight of pregnant rats, fetal biometric, morphological malformation, and skeletal formation. Results: CLE 100 mg/kg BW and 500 mg/kg BW did not cause any change in the number of a living fetus, body weight, and length of fetuses like the comparison group. Both doses of CLE shown have a normal skeletal formation. Resorption was found in the comparison group and CLE 100 mg/kg BW with the percentage was 65.21% and 6.67%. It was found that there is no significant difference (p<0.05) between both doses of CLE compared to control group. Conclusion: From the results, it is concluded that CLE did not have the teratogenic effect.

A COMPARISON OF THE CONCENTRATION OF C14 IN THE TISSUES OF PREGNANT AND NONPREGNANT FEMALE RATS FOLLOWING THE INTRAVENOUS ADMINISTRATION OF VITAMIN K1-C14 AND VITAMIN K3-C14

1957 ◽  
Vol 35 (1) ◽  
pp. 691-697 ◽  
Author(s):  
J. D. Taylor ◽  
G. J. Millar ◽  
R. J. Wood
Keyword(s):  
Skeletal Muscle ◽  
Vitamin K ◽  
Intravenous Administration ◽  
Fetal Liver ◽  
Live Weight ◽  
Fetal Tissue ◽  
Female Rats ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Significant Difference

The C14 content was determined of the livers, spleens, skeletal muscle, blood, feces, and urine of both pregnant and nonpregnant female rats and of the placentas, fetal livers, fetuses, and amnionic fluids of pregnant rats following the intravenous administration of 5 mg./kg. of either vitamin K1-C14 or vitamin K3-C14. The C14 concentrations of the livers of the rats given vitamin Kt were about 24 times larger than those of animals that had received vitamin K3-C14. A fivefold difference in the same direction exists between the concentrations in the spleens of the two groups. The C14 levels for skeletal muscle, blood, placenta, fetal liver, and fetal tissue were of similar magnitude regardless of whether vitamin Kt or vitamin K3 was administered. Isotope dilution tests revealed that following intravenous administration of vitamin K1-C14 the amount of radioactivity present as unchanged vitamin Kt-C14 was 12% for fetal tissue, 59% for placenta, and 120% for the maternal liver. The dry weights of the livers of pregnant rats were larger than those of nonpregnant rats and the increase was proportional to the live weight of the pregnant rat. No significant difference could be demonstrated in the percentage of the injected dose of vitamin K1 deposited in the livers of pregnant or nonpregnant rats. The same was true for vitamin K3-C14. The results of this experiment indicate that vitamin K3-C14 is not concentrated in the liver of the rat whereas vitamin K1-C14 is. Furthermore, it would appear that both vitamin K1 and vitamin K3 can pass the placental barrier of the rat.

scholarly journals Preclinical Trial of Traditional Plant Remedies for the Treatment of Complications of Gestational Malaria

Medicines ◽  
2021 ◽  
Vol 8 (12) ◽  
pp. 79
Author(s):  
Peter Uchenna Amadi ◽  
Emmanuel Nnabugwu Agomuo ◽  
Chinyere Nneka Ukaga ◽  
Uche Chinedu Njoku ◽  
Joy Adaku Amadi ◽  
...  
Keyword(s):  
Malaria In Pregnancy ◽  
Herbal Remedies ◽  
Therapeutic Effects ◽  
Pregnant Rats ◽  
Crown Rump Length ◽  
Preclinical Trial ◽  
Pregnant Rat ◽  
Average Percentage ◽  
Significant Difference ◽  
In Pregnancy

Background: Most pregnant women living in high malaria endemic regions of Nigeria use herbal remedies for the management of malaria-in-pregnancy, rather than the commonly prescribed drugs. Remedies common to this area involve a suspension of A. indica (AI) leaves and in some cases, a suspension containing a mixture of AI and D.edulis (PS). Aim: This study examined the therapeutic efficacies of AI, PS, or a combination of AI and PS in a pregnant rat model for exoerythrocytic stages of Plasmodium falciparum parasite. Method: A predetermined sample size of 30 dams was used (for a power level and confidence interval of 95%), and divided equally into six groups made up of non-malarous dams, untreated malarous dams, and malarous dams either treated exclusively with 1 mL of 3000 mg/kg b.w AI, 1000 mg/kg b.w PS, AI + PS (50% v/v), or 25 mg/kg b.w CQ. Result: No maternal mortality was recorded. AI significantly improved maternal weight gain from 32.4 to 82.2 g and placental weight from 0.44 to 0.53 g. In the curative test, AI and AI + PS significantly reduced the average percentage parasitemia (APP) in the pregnant rats from >80% to <20%. No significant difference in the APP was found between the pregnant rats treated with any of CQ or AI during the suppressive test. Results for the prophylactic test of the study groups showed that the APP was significantly reduced from 24.69% to 3.90% when treated with AI and 3.67% when combined with PS. AI + PS reduced diastolic blood pressure from 89.0 to 81.0 mm/Hg and compared with that of the non malarous dams. AI or AI + PS significantly increased the platelet counts (103 µL) from 214.1 to 364.5 and 351.2, respectively. AI and AI + PS improved birth weight from 2.5 to 3.9 g and crown rump length from 2.6 to 4.1 cm. For biomarkers of preeclampsia, combining AI and PS led to the reversal of the altered levels of creatine kinase, lactate dehydrogenase, cardiac troponin, soluble Fms-Like Tyrosine Kinase-1, and placental growth factor. Conclusions: This study validates the use of A. indica for the treatment of gestational malaria due to its antiplasmodial and related therapeutic effects and in combination with pear seeds for the management of malaria-in-pregnancy-induced preeclampsia.

scholarly journals Loss of anti-contractile effect of perivascular adipose tissue in offspring of obese rats

2016 ◽  
Vol 40 (8) ◽  
pp. 1205-1214 ◽  
Author(s):  
K E Zaborska ◽  
M Wareing ◽  
G Edwards ◽  
C Austin
Keyword(s):  
Adipose Tissue ◽  
Maternal Obesity ◽  
Later Life ◽  
Independent Effect ◽  
Sprague Dawley ◽  
Response Curves ◽  
Perivascular Adipose Tissue ◽  
Contractile Effect ◽  
Sprague Dawley Rats ◽  
Pregnancy And Lactation

Abstract Rationale: Maternal obesity pre-programmes offspring to develop obesity and associated cardiovascular disease. Perivascular adipose tissue (PVAT) exerts an anti-contractile effect on the vasculature, which is reduced in hypertension and obesity. Objective: The objective of this study was to determine whether maternal obesity pre-programmes offspring to develop PVAT dysfunction in later life. Methods: Female Sprague–Dawley rats were fed a diet containing 10% (control) or 45% fat (high fat diet, HFD) for 12 weeks prior to mating and during pregnancy and lactation. Male offspring were killed at 12 or 24 weeks of age and tension in PVAT-intact or -denuded mesenteric artery segments was measured isometrically. Concentration–response curves were constructed to U46619 and norepinephrine. Results: Only 24-week-old HFD offspring were hypertensive (P<0.0001), although the anti-contractile effect of PVAT was lost in vessels from HFD offspring of each age. Inhibition of nitric oxide (NO) synthase with 100 μM l-NMMA attenuated the anti-contractile effect of PVAT and increased contractility of PVAT-denuded arteries (P<0.05, P<0.0001). The increase in contraction was smaller in PVAT-intact than PVAT-denuded vessels from 12-week-old HFD offspring, suggesting decreased PVAT-derived NO and release of a contractile factor (P<0.07). An additional, NO-independent effect of PVAT was evident only in norepinephrine-contracted vessels. Activation of AMP-activated kinase (with 10 μM A769662) was anti-contractile in PVAT-denuded (P<0.0001) and -intact (P<0.01) vessels and was due solely to NO in controls; the AMPK effect was similar in HFD offspring vessels (P<0.001 and P<0.01, respectively) but was partially NO-independent. Conclusions: The diminished anti-contractile effects of PVAT in offspring of HFD dams are primarily due to release of a PVAT-derived contractile factor and reduced NO bioavailability.

Difference in luteal and placental P45017α: substrate preference and hormonal regulation in the rat

1987 ◽  
Vol 115 (3) ◽  
pp. 387-393
Author(s):  
B. Eckstein ◽  
I. Khan ◽  
G. Gibori
Keyword(s):  
Corpus Luteum ◽  
Hormonal Regulation ◽  
Inhibitory Effect ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Substrate Preference ◽  
Corpora Lutea ◽  
Pregnant Rats ◽  
Significant Difference ◽  
Time Point

ABSTRACT The purpose of this study was to assess the substrate specificity of P45017α in both the corpus luteum and placenta of pregnant rats, and to analyse the site at which LH/human chorionic gonadotrophin (hCG) regulates the activities of this enzyme. To distinguish the substrate preference, placentas and corpora lutea were obtained from rats on day 15 of pregnancy. Tissues were homogenized and the 10 000 g supernatants incubated in the presence of equimolar concentrations of [14C]progesterone and [3H]17α-hydroxyprogesterone as substrate with either NADH or NADPH as cofactors for 2, 8, 16 and 24 min. The labelling pattern of both 17α-hydroxyprogesterone and testosterone indicated that the corpus luteum produced testosterone preferentially from progesterone, whereas the placenta principally used 17α-hydroxyprogesterone and synthesized six times as much testosterone from 17α-hydroxyprogesterone than from progesterone. Addition of either NADPH or NADH as cofactors had no effect on substrate preference. The products of the two enzymatic activities were identified by recrystallization to constant 14C/3H ratios. The ratio of 14C/3H in testosterone produced by the corpus luteum was 16-fold higher than in that produced by the placenta. To explore which of the two activities of P45017α is regulated by the gonadotrophin, rats were treated with either 1·5 IU hCG or vehicle between days 13 and 15 of pregnancy. Hydroxylase and lyase activities were determined on day 15 after incubation for 2,8,16 or 24 min in the presence of either NADH or NADPH. Administration of hCG significantly inhibited NADH-dependent 17α-hydroxylase in the placenta at each time-point studied. The inhibition reached 69% at 24 min. Human chorionic gonadotrophin did not affect the NADPH-dependent 17α-hydroxylase and had only a slight inhibitory effect on both NADH- and NADPH-dependent 17,20-lyase activities in the placenta. In contrast to its effect on the placenta, hCG stimulated both NADH- and NADPH-linked 17,20-lyase activities but had no measurable effect on 17α-hydroxylase activities in the corpus luteum. In summary, the results of the present investigation have revealed a significant difference in the behaviour of 17α-hydroxylase/17,20-lyase activities in the placenta and corpus luteum. The substrate preference and the control of both enzyme activities by LH/hCG differs dramatically. J. Endocr. (1987) 115, 387–393

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