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L Poston

Publications and source records attributed to L Poston.

At least 37 records · Page 2Linked to original sources
PubMed2003

Uterine artery function in pregnant rats fed a diet supplemented with animal lard.

We hypothesised that maternal uterine artery vascular dysfunction could contribute to cardiovascular dysfunction in offspring of rats fed a diet rich in fat. Sprague-Dawley rats were fed for 10 days prior to pregnancy and throughout gestation either: (a) a control breeding diet, or (b) the same diet supplemented with 20 % w/w lard, vitamins, essential micronutrients and protein to control values. At 20 days gestation vascular function was assessed in uterine arteries and third-order mesenteric arteries. Vascular reactivity in response to application of potassium, noradrenaline, the thromboxane analogue U46619, acetylcholine and nitric oxide was assessed. Maternal plasma concentrations of factors likely to contribute to endothelial dysfunction were measured. Maximum acetylcholine-induced relaxation was impaired in the mesenteric arteries of the lard-fed dams (max % relaxation: lard-fed, 69.7 +/- 6.48; control, 85.37 +/- 2.69, P = 0.03). Uterine artery vascular function was similar in the two groups (max % acetylcholine-induced relaxation: lard-fed, 73.7 +/- 4.01; control, 77.5 +/- 4.72, P = 0.98). Concentrations of plasma lipids, 8-epi-PGF(2alpha) and leptin were normal, whereas insulin and corticosterone concentrations were raised in the lard-fed group (insulin (ng ml(-1)): lard-fed, 8.04 +/- 0.47; control, 1.35 +/- 0.37, P < 0.0001; corticosterone (ng ml(-1)): lard-fed, 1164.0 +/- 170.9; control, 541.9 +/- 96.3, P = 0.005). Fetal and placental weights were reduced in lard-fed dams (fetus (g): lard-fed, 4.27 +/- 0.38; control, 2.96 +/- 0.40, P = 0.025; placenta (g): lard-fed, 0.72 +/- 0.06; control, 0.57 +/- 0.04, P = 0.05). Cardiovascular dysfunction in offspring is not associated with reduced uterine artery endothelial function but is associated with activation of the hypothalamic-pituitary-adrenal axis, hyperinsulinaemia and fetoplacental growth retardation.

Animal Feed↗
PubMed2002

Liver triacylglycerols and free fatty acids in streptozotocin-induced diabetic rats have atypical n-6 and n-3 pattern.

In diabetes there is a decrease in membrane arachidonic (AA) and docosahexaenoic (DHA) acids and a concomitant increase in linoleic (LA) and alpha-linolenic (ALA) acids. This metabolic perturbation is thought to be due to impaired activity of Delta(6)- and Delta(5)-desaturases. Triacylglycerols are the major lipid pool in plasma and liver tissue and have a significant influence on fatty acid composition of membrane and circulating phospholipids. Data on the distribution of n-6 and n-3 polyunsaturated fatty acids of triacylglycerols in diabetes are sparse. We investigated whether streptozotocin-induced diabetes in Sprague-Dawley rats alters fatty acid composition of triacylglycerols and free fatty acids of liver tissue. The animals were fed a breeding diet prior to mating, during pregnancy and lactation. On days 1-2 of pregnancy, diabetes was induced in 10 of the 25 rats. Liver was obtained at post partum day 16 for analysis. Relative levels of LA (P=0.03), dihomo-gamma-linolenic acid (DHGLA) (P=0.02), AA (P=0.049), total n-6 (P=0.02), ALA (P=0.013), eicosapentaenoic acid (EPA) (P=0.004), docosapentaenoic acid (22:5n-3, DPA) (P=0.013), DHA (P=0.033), n-3 metabolites (P=0.015) and total n-3 (P=0.011) were significantly higher in the triacylglycerols of the diabetics compared with the controls. Similarly, liver free fatty acids of the diabetics had higher levels of LA (P=0.0001), DHGLA (P=0.001), AA (P=0.001), n-6 metabolites (P=0.002), total n-6 (P=0.0001), ALA (P=0.003), EPA (P=0.015), docosapentaenoic (22:5n-3, P=0.003), DHA (P=0.002), n-3 metabolites (P=0.005) and total n-3 (P=0.001). We conclude that impaired activity of desaturases and/or long chain acyl-CoA synthetase could not explain the higher levels of AA, DHA and n-6 and n-3 metabolites in the diabetics. This seems to be consistent with an alteration in the regulatory mechanism, which directs incorporation of polyunsaturated fatty acids either into triacylglycerols or phospholipids.

Acyl-CoA Dehydrogenase, Long-Chain↗
PubMed2002

Molecular identification and localization of Trp homologues, putative calcium channels, in pregnant human uterus.

The mechanisms underlying the switch from uterine quiescence to contractile activity in labour are not clearly understood. Increasing evidence suggests that pathways of myometrial calcium homeostasis, including store-operated calcium entry (SOCE), may play an important role. The molecular basis of the membrane-associated calcium channels contributing to SOCE in pregnant human myometrium is not known, but they are likely to be hetero- or homo-oligomeric assemblies of transient receptor potential channel (TrpC) proteins, encoded by the mammalian homologues of Drosophila Trp genes. This study has therefore determined Trp gene expression and also TrpC protein expression and localization in term pregnant human myometrial tissue and primary cultured human myometrial smooth muscle (HMSM) cells. RT-PCR amplified fragments of Trp1, Trp3, Trp4, Trp6 and Trp7. PCR products were 100% homologous to published human sequences. Western blot analysis detected TrpC1, TrpC3, TrpC4 and TrpC6 proteins, which were of expected size. Immunolocalization revealed TrpC1, TrpC3, TrpC4 and TrpC6 protein expression in myometrial tissue and HMSM cells. TrpC protein immunostaining in HMSM cells was distributed in a distinct reticular fashion. TrpC proteins may be candidate proteins forming SOCE channels in term pregnant human myometrium.

Blotting, Western↗
PubMed2001

Abnormal aortic fatty acid composition and small artery function in offspring of rats fed a high fat diet in pregnancy.

1. Disturbances of the in utero environment are associated with an increased risk of cardiovascular disease in adulthood. In this study we have determined whether abnormal vascular function in the adult offspring of rats fed a high saturated fat diet in pregnancy is associated with altered plasma lipids or vascular fatty acid content. 2. Female Sprague-Dawley rats were fed a breeding diet (4 % fat) or a diet high in saturated fat (20 % fat) for 10 days prior to and throughout pregnancy, and during weaning. Female offspring were then fed a maintenance diet (3 % fat) until 160 days of age. 3. Endothelium-dependent relaxation induced by acetylcholine was blunted in isolated branches of the femoral artery from 160-day-old female offspring of dams fed the saturated fat diet when compared with female offspring of dams fed the breeding diet. These offspring exhibited elevated plasma triglyceride and reduced plasma high density lipoprotein cholesterol concentrations. 4. The fatty acid composition of the aortas was abnormal, with a marked reduction in the content of arachidonic and docosahexaenoic acids. 5. This study demonstrates that a high fat diet in pregnant rats produces abnormal vascular function, plasma lipid disturbances and altered vascular fatty acid content in their female offspring during adulthood.

Animals↗
PubMed2001

Dietary restriction in pregnant rats causes gender-related hypertension and vascular dysfunction in offspring.

We have investigated the effects of moderate global undernutrition during gestation in the rat on the blood pressure of male and female offspring, and on the development of systemic vascular function. Pregnant Wistar rats were nutritionally restricted (R) by feeding with 70% of the normal gestation-matched dietary intake from 0 to 18 days gestation.R offspring were growth retarded at birth but of similar weight to controls (C) at 20 days. Systolic and/or diastolic and mean arterial blood pressures, measured directly by femoral artery catheter, were elevated from 60 days onward in male R offspring (mean arterial pressure: day 60, P < 0.01; day 100, P < 0.05; day 200, P < 0.005, R vs. C), and from 100 days onward in female R offspring (mean arterial pressure day 100 and day 200, P < 0.05; R vs. C). Maximal constriction to phenylephrine (PE) (P < 0.05) and to noradrenaline (NA) (P < 0.05) was reduced in isolated femoral arteries of day 20 R pups. These differences did not persist into adulthood. In male adult R offspring (200 days), maximal vasoconstriction to the thromboxane A2 mimetic, U46619 (P < 0.05) and sensitivity to potassium (P < 0.01) were enhanced. Moderate maternal undernutrition in rat gestation adversely affects cardiovascular function in the offspring. These abnormalities increase with age and are more pronounced in males.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2001

Validation of the Welch Allyn 'Vital Signs' oscillometric blood pressure monitor.

This study has determined the accuracy of the Welch Allyn 'Vital Signs' blood pressure (BP) monitoring device in an adult population, according to the criteria of the British Hypertension Society (British Hypertension Society, 1993). Validation was also classified by the American 'Association for the Advancement of Medical Instrumentation' (AAMI). The Welch Allyn 'Vital Signs' monitor achieved a BHS grade A for both systolic and diastolic BP. It also met the criteria for the AAMI protocol. The mean differences between trained observers using a mercury sphygmomanometer and the device were -1 +/- 5 mm Hg for systolic BP and -3 +/- 4 mm Hg for diastolic BP. The Welch Allyn 'Vital Signs' monitor can be recommended for clinical use in the adult population. This is one of the first oscillometric monitors designed for routine use in a hospital environment that has been found to provide an accurate assessment of BP by accepted validation procedures.

Adult↗
PubMed2001

Developmental changes in reactivity of small femoral arteries in the fetal and postnatal baboon.

OBJECTIVE: We evaluated in vitro responsiveness of small arteries (internal diameter, 300 microm) from the femoral vascular bed of normal fetal (0.75-1.0 gestation) and neonatal (43-46 days) baboons to investigate whether the transition from fetal to neonatal life was associated with functional alterations in vasoconstrictor and vasodilator responses. STUDY DESIGN: The maximum response and sensitivity to potassium and to the constrictor agonists norepinephrine and U46619 (a thromboxane mimetic) were studied by in vitro myography. Vasodilator responses to the endothelium-dependent dilators acetylcholine and bradykinin were also investigated. RESULTS: The maximum response to norepinephrine and U46619 and to potassium increased with gestational age, whereas the sensitivity to these vasoconstrictors was similar in all groups studied. In contrast, acetylcholine- and bradykinin-induced relaxation (median effective concentration and maximum response) did not change with age. CONCLUSION: Receptor-mediated responses to a catecholamine, a prostanoid, and 2 endotheliumdependent vasodilators are similar in the fetal and neonatal baboon. The increase in maximal constriction with development, which is probably associated with growth or maturation of vascular smooth muscle, is likely to be a functionally important aspect in the development of cardiovascular function.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2001

Is oxidative stress involved in the aetiology of pre-eclampsia?

Pre-eclampsia is one of the major indications for elective premature delivery. Several lines of evidence suggest that pre-eclampsia is associated with a state of oxidative stress, offering hope of prevention by antioxidant supplementation. It was recently shown by the present authors that supplementation with vitamin C and E from early in pregnancy leads to a reduction in the incidence of the disease in "high-risk" women.

Antioxidants↗
PubMed2001

Placentation, antiphospholipid syndrome and pregnancy outcome.

The antiphospholipid antibodies (aPLs) are a diverse group of autoantibodies associated with a pattern of disease known as antiphospholipid syndrome (APS). Pregnancy complications secondary to placental insufficiency are key features of this disease. The mechanisms underlying the placental pathology remain unclear. In this article the process of placentation in healthy and pathological pregnancies is reviewed. The evidence for defective placentation in APS pregnancies and involvement of aPLs in this process is summarized. Finally hypotheses based on the interpretation of these studies are discussed.

Antiphospholipid Syndrome↗
PubMed2001

Activity and expression of soluble and particulate guanylate cyclases in myometrium from nonpregnant and pregnant women: down-regulation of soluble guanylate cyclase at term.

The role of cGMP in the regulation of human myometrial smooth muscle contractility is at present unclear. cGMP can be synthesized by a cytoplasmic, soluble guanylate cyclase (sGC), which is stimulated by nitric oxide and carbon monoxide, and by particulate membrane-bound GC, which are activated by natriuretic peptides. The aim of this study was to determine whether sGC or pGC are present in nonpregnant and pregnant human myometrium, and whether the activity and expression of these enzymes and the cGMP content change during pregnancy and with labor. Myometrium was obtained from nonpregnant women (n = 12) and pregnant women who were preterm (25-34 wk gestation; n = 12), term (>38 wk) not in labor (n = 14), or term in active labor (n = 12). The cGMP content in myometrium obtained from preterm deliveries was significantly higher than that in tissue obtained from nonpregnant women and decreased at term, especially in laboring groups. Protein and mRNA for sGC, particulate GC-A, GC-B, and the clearance receptor were detected in human myometrium. cGMP in pregnant human myometrium, however, appears to be produced predominantly by sGC and possibly by GC-B, as GC-A was only weakly expressed. sGC activity was greater in myometrium from preterm (nonlabor) deliveries compared those taken at term (in labor), but was down-regulated compared with activity in nonpregnant myometrium. Neither atrial natriuretic peptide nor C-type natriuretic peptide (agonists for GC-A and GC-B, respectively) altered contractility in vitro of myometrium from women at term (not in labor). We conclude that the cGMP/guanylate cyclase system in human myometrium is gestationally regulated and potentially plays an important role in mediating quiescence during early pregnancy. A reduction in cGMP availability may contribute to the switch to contractile activity at term.

Atrial Natriuretic Factor↗
PubMed2000

A novel family of S-nitrosothiols: chemical synthesis and biological actions.

S-Nitrosothiols are a class of chemical compounds that decompose to release nitric oxide and show promise in the treatment of a variety of cardiovascular diseases. Some of these are present in vivo and others have been synthesized in vitro. However, those discovered or synthesized to date have very little tissue selectivity or specificity. We synthesized a number of novel S-nitrosated dipeptides of high purity and examined their effects on vasorelaxation using rat mesenteric arteries and on inhibition of platelet aggregation using platelets from healthyhuman subjects. For comparison, we also tested the effects of S-nitroso-l-glutathione (GSNO, an S-nitrosothiol present in vivo) and S-nitroso-N-acetyl-d-beta,beta-dimethylcysteine (SNAP(D), the d-isomer of SNAP, a commonly used S-nitrosothiol previously synthesized in vitro) in these biological systems. Satisfactory elemental analyses were obtained for all compounds synthesized (less than +/- 0.3%), and all accurate mass measurements were within 1-5 ppm of the expected mass. The novel S-nitrosated dipeptides all elicited vasorelaxation with significantly higher potency, of the order of one log molar unit, than either GSNO or SNAP(D). However, all compounds inhibited U46619-induced platelet aggregation with similar potency to GSNO and SNAP(D). These findings indicate a degree of tissue selectivity which may prove to be of therapeutic usefulness.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2000

Modulation of vascular tone by nitric oxide and endothelin 1 in myometrial resistance arteries from pregnant women at term.

OBJECTIVE: We evaluated the role of endothelium-derived nitric oxide and endothelin 1 in the modulation of myogenic tone, norepinephrine-induced tone, and flow-mediated responses in resistance arteries from pregnant women at term. STUDY DESIGN: Arteries (approximately 200 microm at 50 mm Hg; n = 27) were dissected from myometrial biopsies obtained from women undergoing elective cesarean delivery at term and mounted in a pressure arteriograph. Responses to intraluminal flow, pressure, and norepinephrine were studied in the absence and presence of the nitric oxide synthase inhibitor Nomega-nitro-L-arginine and the endothelin-converting enzyme inhibitor phosphoramidon. RESULTS: Pressure-induced (80 mm Hg) myogenic tone was significantly enhanced after incubation with Nomega-nitro-L-arginine (33% +/- 8% vs 24% +/- 4%; P <.05), whereas phosphoramidon significantly reduced myogenic tone (24% +/- 5% vs 33% +/- 5%; P <.05). A combination of Nomega-nitro-L -arginine and phosphoramidon did not affect myogenic tone. Norepinephrine-induced tone was significantly enhanced after nitric oxide synthase inhibition (49% +/- 6% vs 41% +/- 5%; P <.05) but was not affected by phosphoramidon. Flow-mediated dilatation was increased in the presence of phosphoramidon compared with flow-induced dilatation in physiologic salt solution (maximum dilatation, 57% +/- 12% vs 30% +/- 5%; analysis of variance, P <.05), and all flow-induced dilatation was abolished by Nomega-nitro-L -arginine. CONCLUSIONS: Nitric oxide and endothelin 1 may play a significant role in modulation of myogenic tone and flow-mediated responses in the resistance vasculature of the uterine circulation in normal pregnancy.

Arteries↗
PubMed2000

Increase of the isoprostane 8-isoprostaglandin f2alpha in maternal and fetal blood of rats with streptozotocin-induced diabetes: evidence of lipid peroxidation.

OBJECTIVE: Pregnancy complicated by diabetes is associated with maternal complications and fetal abnormalities. Animal models of diabetes suggest that heightened free radical production may be implicated in the pathogenesis of this condition. The purpose of this investigation was to evaluate oxidative stress in plasma from diabetic rats and their fetuses through measurement of concentrations of 8-isoprostaglandin F(2alpha), a stable marker of lipid peroxidation. STUDY DESIGN: Diabetes was induced in virgin and pregnant rats with streptozotocin. Blood samples were collected after 20 days of diabetes. Adult and fetal plasma 8-isoprostaglandin F(2alpha) concentrations were determined by gas chromatography-mass spectroscopy. RESULTS: Significantly higher plasma 8-isoprostaglandin F(2alpha) concentrations were observed in the virgin rats with diabetes and in both the pregnant dams with diabetes and their fetuses when compared with their respective control groups without diabetes (P <.001). CONCLUSION: Oxidative stress was induced in both mother and fetus in rodent pregnancy complicated by diabetes. This finding may have implications for fetal dysmorphogenesis and in fetal programming for adulthood disease.

Animals↗
PubMed2000

Effects of undernutrition in early pregnancy on systemic small artery function in late-gestation fetal sheep.

OBJECTIVE: The aim of this study was to investigate functional development of small arteries from the skeletal circulation of fetal sheep and to determine whether maternal undernutrition affects responses to vasoconstrictive and vasodilatory agonists in arteries from the late-gestation fetus. STUDY DESIGN: We investigated vasoconstrictive and vasodilatory responses of isolated small (approximately 300 microm) arteries from the femoral vascular bed of fetal sheep and from late-gestation pregnant ewes. Ewes were fed either 100% of the nutritional requirement throughout pregnancy (control group) or a restricted diet of 85% or 50% of the nutritional requirement for the first 70 days of pregnancy. For the remainder of pregnancy all ewes were fed the complete diet. RESULTS: Among control group animals vasoconstriction in response to norepinephrine was well developed in fetuses at 0.6 and 0.9 gestation with respect to that in the ewes. When expressed as a percentage of the response to 125-mmol/L potassium (to correct for differences in vessel size and muscle mass), maximum constriction in response to norepinephrine was greater in fetal vessels from 0.9 gestation than in either those at 0.6 gestation or those of the ewes. Endothelium-dependent vasorelaxation responses to acetylcholine and bradykinin were also well developed in fetuses at 0.6 and 0.9 gestation and were similar to those in the ewes. In fetuses at 0.9 gestation the 50% nutritional restriction of the ewe led to blunted endothelium-dependent vasodilatation in response to acetylcholine and blunted endothelium-independent vasodilatation in response to sodium nitroprusside. Responses in the fetuses at 0.9 gestation in which the ewes were fed a restricted diet of 85% were normal. CONCLUSION: This study shows that from midgestation onward small arteries from the skeletal circulation of the fetal sheep have the functional capacity to respond to norepinephrine and endothelium-dependent vasodilators (eg, acetylcholine and bradykinin). The blunted responses to acetylcholine and sodium nitroprusside in the fetuses at 0.9 gestation among the group of dietarily restricted ewes (restricted diet of 50% group) were indicative of impaired vascular smooth muscle sensitivity to nitric oxide. This defect may contribute to the development of hypertension in later life.

Acetylcholine↗
PubMed2000

Calcium homeostatic pathways change with gestation in human myometrium.

A rise in intracellular calcium is the primary trigger for contractile activity in pregnant human myometrium. It is hypothesized that key proteins involved in myometrial calcium homeostasis are gestationally regulated and play an important role in the preparation for labor. The aims of the study were to investigate the role of sarcoplasmic reticulum Ca ATPases (SERCAs) in regulating spontaneous contractile activity in myometrium, and to determine the expression of SERCA isoforms 2a and 2b, and the plasma membrane Ca ATPase (PMCA), at term and during labor. Western blot analysis demonstrated that the expression of SERCA 2a and 2b significantly increased in myometrium of women in labor compared with those not in labor. The augmentation of contractile activity in laboring myometrium in the presence of a SERCA 2 inhibitor, cyclopiazonic acid (CPA), demonstrated the functional significance of this observation. It is interesting that the application of CPA in the presence of a calcium-activated potassium channel inhibitor to term nonlabor myometrium mimicked the response of myometrium from women in active labor to CPA alone. We conclude that the activity of SERCA isoforms becomes increasingly important in the maintenance of regular contractile activity during labor and may compensate for the functional loss of other calcium control pathways at term.

Blotting, Western↗
PubMed2000

A validation of the Mobil O Graph (version 12) ambulatory blood pressure monitor.

OBJECTIVE: To assess the clinical accuracy of the Mobil O Graph (version 12) ambulatory blood pressure monitor in an adult population. METHODS: The accuracy of the device was assessed by predefined criteria (British Hypertension Society, BHS) in 85 subjects recruited from the patients and staff in a teaching hospital. A series of same-arm sequential blood pressure measurements were taken: first two observers taking simultaneous mercury readings, followed by a reading with the Mobil O Graph ambulatory monitor. A total of seven readings were taken from each subject in the sitting position. The data were then analysed according to the BHS protocol and the criteria of the Association for the Advancement of Medical Instrumentation (AAMI). RESULTS: The Mobil O Graph ambulatory monitor fulfilled the criteria of the BHS protocol, achieving a grade B for systolic blood pressure (SBP) and a grade A for diastolic blood pressure (DBP). The mean differences were -2+/-8 mmHg for SBP and -2+/-7 mmHg for DBP. The device therefore also passed the AAMI standard (the mean to be within 5+/-8 mmHg). CONCLUSION: The Mobil O Graph ambulatory monitor performed in a satisfactory manner according to the BHS and the AAMI criteria and can therefore be recommended for clinical use in the general population.

Adolescent↗