Biomedical subjects

Philip N Baker

Publications and source records attributed to Philip N Baker.

45 records · Page 3Linked to original sources

PubMed2003

Myometrial and placental artery reactivity alone cannot explain reduced placental perfusion in pre-eclampsia and intrauterine growth restriction.

OBJECTIVES: (1) To investigate a possible association between myometrial and placental artery vasoreactivity and perfusion at the basal and chorionic plates, respectively. (2) To confirm that myometrial arteries from women with pre-eclampsia and intrauterine growth restriction exhibit an attenuated endothelium-dependent vasodilatory response. METHODS: Women with normal pregnancy, pre-eclampsia and intrauterine growth restriction had a magnetic resonance scan to assess placental perfusion using a technique called intravoxel incoherent motion. At delivery, myometrial and chorionic plate placental arteries were assessed on a wire myograph. Vessels were pre-constricted with the thromboxane mimetic U46619 and dilated with incremental doses of bradykinin. RESULTS: Pre-constricted myometrial arteries from women with pre-eclampsia or intrauterine growth restriction exhibited an attenuated vasodilatory response to bradykinin, compared with normal pregnancy (P < 0.0001). Pre-constricted placental arteries exhibited a minimal vasodilatory response in all three groups of women (P = 0.10). Maximal constrictor and vasodilatory responses of myometrial arteries were not associated with the perfusing fraction at the basal plate. Maximal constrictor and vasodilatory responses of chorionic plate placental arteries were not associated with the perfusing fraction at the chorionic plate. CONCLUSION: We confirm that myometrial arteries from women with pre-eclampsia or intrauterine growth restriction exhibit an attenuated endothelium-dependent vasodilatory response. Apart from vasoreactivity of small arteries, other factors may be involved in the control of placental perfusion.

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

PubMed2002

Vascular adaptations to pregnancy in mice: effects on myogenic tone.

The mechanisms underlying vascular adaptations in pregnancy remain to be fully elucidated. One of the contributory mechanisms for reduced vascular tone may be a reduction of myogenic tone. Myogenic tone was assessed as the difference between internal diameter in the presence and absence of external calcium at different intramural pressure steps (60-100 mmHg). Myogenic responses were reduced in resistance-sized mesenteric and main uterine arteries in late pregnant compared with nonpregnant C57BL/6J mice. In vessels from pregnant, but not nonpregnant mice, the myogenic response was enhanced by preincubation with nitric oxide (NO) synthase inhibitor N(G)-nitro-l-arginine methyl ester, was further elevated by the gap junction inhibitor 18-alpha glycyrrhetinic acid, but was unaltered by the prostaglandin H synthase inhibitor meclofenamate. Endothelium removal enhanced myogenic tone only in the vessels from pregnant animals, thus confirming the role of the endothelium in modulating myogenic tone in pregnancy. These results suggest that endothelium-derived NO as well as gap junction communications modulate myogenic tone in mouse pregnancy.

Adaptation, Physiological↗

PubMed2002

The role of gap junctions in mediating endothelium-dependent responses to bradykinin in myometrial small arteries isolated from pregnant women.

Endothelium-dependent responses were assessed in myometrial small arteries isolated from pregnant women, using pressure myography. Responses to bradykinin were unaffected by the combined presence of the nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME, 100 micro M) and the cyclo-oxygenase inhibitor, indomethacin (10 micro M). The additional presence of clotrimazole (50 micro M) attenuated, but did not abolish, vasodilator responses to bradykinin. Raising extracellular [K(+)] (by between 1 and 15 mM) did not evoke a vasodilator response, nor did the cannabinoids, anandamide and methanandamide. Responses to bradykinin were attenuated in the presence of the gap junction inhibitors 18-alpha-glycyrrhetinic acid (18-alpha GA, 100 micro M), carbenoxolone (100 micro M) and palmitoleic acid (50 micro M). SR141716A, the CB(1) receptor antagonist attenuated responses to bradykinin, but only at high concentrations (10 micro M). These results suggest that gap junctional communication is involved in the nitric oxide (NO)- and prostanoid-independent vasodilator responses to bradykinin in myometrial small arteries in normal pregnancy.

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

PubMed2002

Differential mechanisms of endothelium-dependent vasodilator responses in human myometrial small arteries in normal pregnancy and pre-eclampsia.

Pre-eclampsia is a pregnancy-specific disorder associated with hypertension and proteinuria, characterized by alterations in endothelial cell function. In the present study we have compared responses to the endothelium-dependent vasodilator, bradykinin, in small myometrial arteries from normal pregnant and non-pregnant women and women with pre-eclampsia, in order to assess the relative contributions of nitric oxide, endothelium-derived hyperpolarizing factor (EDHF) and prostanoids in mediating endothelium-dependent vasodilatation. Bradykinin-induced concentration-dependent relaxation in arteries isolated from the three subject groups did not differ with regard to sensitivity or maximum response. Responses to bradykinin in all three groups were unaffected by cyclo-oxygenase inhibition alone, and were similarly unaffected by partial depolarization. The nitric oxide synthase (NOS) inhibitor, N-nitro-l-arginine methyl ester, significantly attenuated the responses to bradykinin in arteries from non-pregnant women and almost abolished responses in arteries from women with pre-eclampsia. However, in arteries from normal pregnant women, bradykinin-induced responses were maintained in the presence of NOS inhibition. Inhibition of NOS combined with partial depolarization abolished responses to bradykinin in these vessels. These results support the suggestion that, in the absence of NO, an EDHF can mediate vasodilator responses to bradykinin during normal pregnancy, an effect not apparent in arteries from non-pregnant women or women with pre-eclampsia. The up-regulation of EDHF-type function may represent a vascular adaptation to normal pregnancy that is absent in pre-eclampsia, and this might contribute to the clinical features of the disease.

Adult↗

PubMed2002

No difference in structure between omental small arteries isolated from women with preeclampsia, intrauterine growth restriction, and normal pregnancies.

OBJECTIVE: Our purpose was to investigate whether there were structural differences between omental small arteries isolated from women with preeclampsia and intrauterine growth restriction and those isolated from women with normal pregnancy. STUDY DESIGN: A pressure myograph was used to study omental small arteries isolated from women with normal pregnancy and women with preeclampsia and intrauterine growth restriction (n = 16, 13, and 8, respectively). With the use of a transilluminating system, lumen diameter, wall thickness, wall/lumen ratio, distensibility, and the stress-strain relationship were studied through pressure ranges of 5 to 100 mm Hg. Arteries were then fixed with glutaraldehyde at the predelivery mean arterial pressure and embedded in epoxy resin. One-micrometer transverse sections were cut for more detailed morphologic examination. RESULTS: Wall thickness, lumen diameter, wall/lumen ratio, distensibility, and the stress-strain relationship of omental small arteries did not differ between patient groups (P >.05; repeated-measures analysis of variance). Detailed histologic examination confirmed these findings. CONCLUSIONS: Alterations in systemic vascular resistance associated with compromised pregnancies are unlikely to result from or produce an alteration in the structure of omental small arteries.

Adult↗

PubMed2002

Functional characteristics of chorionic plate placental arteries from normal pregnant women and women with pre-eclampsia.

OBJECTIVES: We aimed to compare placental small artery function from women with pre-eclampsia and normal pregnancy. In particular, we wished to test the hypothesis that these arteries respond differently to an endothelium-dependent vasodilator, to the presence of nitric oxide, and to the presence of cyclic monophosphate nucleotides. METHODS: A small vessel wire myograph was used to study placental arteries (200 to 550 microm). Contractile function was assessed with vasopressin. Relaxation was assessed with the endothelium-dependent vasodilator, bradykinin, and the endothelium-independent vasodilators sodium nitroprusside (a nitric oxide donor) and papaverine (a phosphodiesterase inhibitor). RESULTS: The constrictor response to vasopressin did not differ between patient groups (p=0.79; repeated measures ANOVA). For both normal pregnancy and pre-eclampsia, the response of pre-constricted arteries to the endothelium-dependent vasodilator, bradykinin, was minimal. Vasorelaxation to sodium nitroprusside and papaverine was attenuated in pre-eclampsia compared to normal pregnancy (p=0.03 and p<0.001, respectively; repeated measures ANOVA). CONCLUSIONS: In pre-eclampsia, placental arteries exhibit an attenuated vasodilatory response to nitric oxide.

Adult↗

PubMed2002

Hypertensive diseases and eclampsia.

Worldwide, pre-eclampsia and eclampsia contribute to the death of a pregnant woman every 3 min. In the UK in recent decades, hypertensive disorders of pregnancy have remained one of the leading causes of both maternal and perinatal morbidity and mortality. The management of pregnancies complicated by hypertension has not significantly altered for many years, possibly as a result of little progress being made in our understanding of the condition. New insights, however, have recently been gained into the pathophysiology of pre-eclampsia. These have yet to be translated into new interventions or to make any impact on clinical management of these pregnancies. This review will therefore focus on recent advances relating to research into the aetiology and pathogenesis of pre-eclampsia, but will conclude with a brief update on current therapeutic strategies.

Antihypertensive Agents↗

PubMed2002

Rescue of trophoblast apoptosis by parathyroid hormone-related protein.

The effects of the 1-34 N-terminal parathyroid hormone-related protein fragment (0-10 microM) and the 67-86 parathyroid hormone-related protein fragment (0-10 microM) on trophoblast apoptosis, induced by TNFalpha and IFN-gamma or by the protein kinase inhibitor staurosporine, were investigated. TNFalpha/IFN-gamma and staurosporine significantly increased the rate of apoptosis by fivefold and by eightfold, respectively. Parathyroid hormone-related protein (1-34) evoked a dose-dependent rescue of both TNFalpha/IFNgamma-induced and staurosporine-induced apoptosis, whereas parathyroid hormone-related protein (67-86) had no significant effect on staurosporine-induced apoptosis, and only significantly diminished TNFalpha/IFNgamma-induced apoptosis at 10 microM. Parathyroid hormone-related protein was thus found to be a cytotrophoblast apoptosis survival factor.

Adult↗

PubMedDate not supplied

Tissue transglutaminase expression and activity in placenta.

Tissue transglutaminase (tTG) expression, distribution and activity were examined in human placenta and derived cells. Immunochemical techniques and RT-PCR were used to demonstrate tTG protein and mRNA in stromal cells and trophoblast in first trimester and at term, with higher levels later in pregnancy. Decidual cells also produce tTG. The data were confirmed using primary cultures of trophoblast, fibroblasts and decidual stromal cells. Substrate incorporation studies indicated tTG activity in association with fibroblast extracellular matrix and the syncytial microvillous membrane (MVM), where several target polypeptides could be observed. tTG is a major autoantigen in Coeliac disease (CoD) which is associated with poor pregnancy outcome. tTG at the placental MVM is a plausible target of maternal autoantibody action.

Biotinylation↗