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Objective: Flow-induced vasodilatation may contribute to lowering of peripheral resistance to pregnancy. This study investigated modulation of flow responses by 17beta-estradiol., Study Design: Small mesenteric arteries from prepubertal female Wistar rats were pretreated for 3 hours with 17beta-estradiol (10(-7) mol/L) with 17alpha-estradiol (10(-7) mol/L) or vehicle (0.1% dimethylsulfoxide). Responses to intraluminal flow were evaluated with use of a pressure arteriograph., Results: After pretreatment with 17beta-estradiol arteries relaxed to flow, whereas those treated with vehicle or 17alpha-estradiol did not (percent change in diameter at maximum flow rate after 17beta-estradiol 38.7% +/- 5.7%, n = 10, vs 1.1% +/- 4.3%, n = 10 after vehicle; p < 0.01). Endothelium removal or pretreatment with either a nitric oxide synthase inhibitor or a novel soluble guanylyl cyclase inhibitor diminished the response to 17beta-estradiol., Conclusion: 17Beta-estradiol stimulated nitric oxide-mediated flow-induced relaxation. Through this pathway 17beta-estradiol could play an important role in the control of vascular tone.

Objective: Our purpose was to evaluate flow-induced responses, myogenic tone, and norepinephrine-induced constriction in myometrial resistance arteries from normal term pregnant women and the role that nitric oxide and prostanoids may play in these responses., Study Design: Arteries (approximately 200 microns, n = 14, at 40 mm Hg) were dissected from myometrial biopsy specimens from women undergoing cesarean section and then were mounted in a pressure arteriograph. Responses to intraluminal flow, pressure, and a constrictor agonist (norepinephrine 10(-6) mol/L) were studied in the absence and presence of N omega-nitro-L-arginine methyl ester (n = 7) or indomethacin (n = 5). Myogenic and norepinephrine-induced tone were calculated after the determination of artery diameter in the absence of extracellular calcium., Results: Arteries developed myogenic tone (80 mm Hg) that was not modulated by nitric oxide or prostanoid release, whereas norepinephrine-induced tone was significantly enhanced by the nitric oxide inhibitor. An increase in intraluminal flow led to dilatation in physiologic salt solution and indomethacin, but to constriction in the presence of N omega-nitro-L-arginine methyl ester (percent increase in diameter at flow rate of 184.6 microliters/min, 24% +/- 8% in physiologic salt solution and 20% +/- 4% in the presence of indomethacin versus -27% +/- 12% in N omega-nitro-L-arginine methyl ester alone and -21% +/- 10% in indomethacin and N omega-nitro-L-arginine methyl ester, respectively, analysis of variance, p < 0.05)., Conclusions: Flow-induced shear stress is a physiologic modulator of vascular tone in myometrial arteries from pregnant women. Nitric oxide, but not prostanoids, mediates this response and also blunts norepinephrine constriction. Nitric oxide may play a fundamental role in the maintenance of adequate blood supply to the fetus during human pregnancy.

Endothelium-derived nitric oxide is proposed to play an important role in the lowering of peripheral vascular resistance in normal pregnancy. In women with preeclampsia, the function of the endothelium is compromised, and it is suggested that reduced nitric oxide synthesis may contribute to the elevation of blood pressure and activation of coagulation pathways. In this study, we have compared responses to increments of intraluminal flow, considered to be a physiological stimulus to nitric oxide release, in arteries from normotensive nonpregnant and pregnant women and women with preeclampsia. Small subcutaneous arteries from normotensive pregnant women showed substantial flow-induced relaxation, which was attenuated by the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) (mean relaxation, 48.3+/-8.0% [absence of L-NAME] versus 19.2+/-10.6% [presence of L-NAME]), whereas those from nonpregnant women and women with preeclampsia demonstrated modest constriction (mean constriction, 10.1+/-7.3% and 1.2+/-7.2%, respectively). Shear stress, the frictional force that is the stimulus for flow responses, was calculated from parameters of flow, viscosity, and artery diameter. Arteries from pregnant women showed greater relaxation to shear than those from nonpregnant women or those with preeclampsia. We conclude that flow-induced shear stress is a potent stimulus to vasodilatation in arteries from pregnant women and that this mechanism may lead to a fall in peripheral vascular resistance in normal pregnancy. Failure of this flow-induced dilatation may contribute to the gestational hypertension of preeclampsia.

Objective: To investigate the hypothesis that, should there be an increase in deported syncytiotrophoblast microvillous membrane fragments in pre-eclampsia, it may cause maternal vascular endothelial dysfunction., Design: Syncytiotrophoblast microvillous membrane (STBM) vesicles, prepared from normal term placentae, were perfused through small subcutaneous arteries isolated from fat biopsies obtained at caesarean section. Endothelial function of these arteries was studied by determining acetylcholine-induced relaxation after preconstriction with noradrenaline. As controls, physiological buffer or red blood cell membranes in physiological buffer were used and endothelial function similarly estimated. Transmission electron microscopy was performed on arteries after perfusion., Sample: STBM vesicles, isolated from the placentae of three healthy women undergoing elective caesarean section for reasons unrelated to pre-eclampsia, were suspended in physiological buffer. Subcutaneous fat arteries were obtained from a separate group of 13 normotensive pregnant women, also undergoing elective caesarean section at term., Results: Perfusion with red blood cell membranes or physiological buffer had no significant effect on the concentration dependent relaxation in arteries preconstricted with noradrenaline. However, after 2 h perfusion with STBM vesicles, arteries showed a significant reduction in relaxation to acetylcholine, indicative of altered endothelial function. Transmission electron microscopy of arteries perfused with STBM vesicles confirmed endothelial disruption., Conclusions: STBM vesicle perfusion specifically altered the relaxation response of preconstricted maternal subcutaneous fat arteries to acetylcholine, suggesting an alteration in endothelial dependent relaxation. Deported microvilli may therefore be capable of producing endothelial cell damage and endothelial dysfunction observed in the maternal syndrome of pre-eclampsia.

1. The mechanisms of vascular adaptation to pregnancy remain to be fully elucidated. In this study we have compared flow-induced dilatation and myogenic responses in fifth generation mesenteric arteries from late pregnant and non-pregnant Wistar rats. 2. Myogenic tone, assessed as the difference between internal diameter (i.d.) in the presence and absence of external calcium, at each of six transmural pressure steps (40-90 mmHg) was no different in arteries from pregnant and non-pregnant animals (90 mmHg; pregnant animals, 20.5 +/- 3.2% change in i.d., n = 13; non-pregnant animals, 14.4 +/- 4.4% change in i.d., n = 13; n.s.). 3. Flow-induced dilatation was significantly increased in arteries from pregnant animals when compared with that in non-pregnant animals (pregnant, 11.2 +/- 3.7% increase in i.d., n = 12; non-pregnant, 1.2 +/- 1.0%, n = 8; P < 0.02; at the maximal flow rate of 1.46 microliters s-1). 4. Flow-induced dilatation was significantly reduced in arteries from pregnant rats after incubation with the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (11.2 +/- 3.7% increase in i.d. vs. 0.8 +/- 1.5% with L-NAME, n = 12, at a flow rate of 1.46 microliters s-1; P < 0.02), but not altered in non-pregnant rats (1.2 +/- 1.0% vs. 1.4 +/- 1.5% with L-NAME, n = 8; n.s.). This was also reflected in a greater response to shear stress in the arteries from pregnant animals. 5. We conclude that myogenic tone is not significantly different in pregnant and non-pregnant resistance sized mesenteric arteries of Wistar rats. However, flow-induced dilatation, mediated by nitric oxide release, may play a major role in lowering vascular resistance during pregnancy.

Objectives: Responses to pressure, agonist-induced constriction, endothelium-dependent vasodilators, and shear stress were investigated in resistance-sized mesenteric arteries in vitro from late-pregnant and nonpregnant rats., Study Design: Myogenic tone was determined in arteries mounted on a pressure myograph by evaluating the response to incremental increases in luminal pressure in resting arteries and arteries preconstricted with norepinephrine (10(-6) mol/L). Flow-mediated dilation was also investigated in the presence and absence of a nitric oxide synthase inhibitor, L-N(omega)-nitro-L-arginine methyl ester. Constrictor responses to norepinephrine (10(-9) to 10(-5) mol/L), were examined with a small vessel myograph. Responses of preconstricted arteries to acetylcholine (10(-9) to 10(-5) mol/L), bradykinin (10(-9) to 10(-5) mol/L), and sodium nitroprusside (10(-9) to 10(-5) mol/L) were also assessed., Results: Myogenic tone was only demonstrable in response to increasing pressure when arteries were preconstricted with norepinephrine (10(-6) mol/L) and was similar in arteries from both pregnant and nonpregnant rats. Flow-mediated dilation was greater in pregnant rats and was reduced by L-N(omega)-nitro-L-arginine methyl ester. Arteries from the pregnant rats demonstrated a reduced constrictor response to norepinephrine. Responses to acetylcholine were similar in both groups, but arteries from the pregnant rats showed enhanced relaxation to bradykinin., Conclusions: The data substantiate previous studies indicating reduced constrictor responses in pregnancy but provide no evidence to suggest that blunted myogenic responses contribute to reduced vascular resistance in pregnancy. The results indicate that flow-mediated nitric oxide release may contribute to vasodilation in pregnant rats. Different responses to two endothelium-dependent vasodilators suggest that specific alterations in signal transduction pathways may influence nitric oxide synthesis in pregnancy.

Objective: To evaluate a multidisciplinary women-only clinic (WOC) providing HIV testing, HIV follow-up, genitourinary screening and a substance misuse service. The clinic is designed to attract women who are at risk of acquiring sexually transmitted infections, including HIV, yet are not using existing medical services., Design: A questionnaire survey and review of the case notes of women attending the WOC during the first seven months (April to October 1991) and comparison with a mixed-sex, daytime genitourinary clinic (John Hunter Clinic), and a HIV out-patients clinic (Kobler Centre) all within St Stephen's Clinic., Results: One hundred and twenty-nine women attended the WOC over the seven month period and 113 completed a questionnaire. The main reasons for attendance included a preference to be seen by a female doctor and staff, the presence of female patients in the waiting area, and the greater convenience of an evening clinic. In the absence of the WOC over half the patients (56%) indicated that they would not have attended a genitourinary medicine (GUM) clinic. The WOC attracted significantly more new patients than in the JHC (31.5% vs 15% p < 0.001). One hundred and four women (81%) were screened for genitourinary infection. Compared with the JHC there were significantly more cases of genital warts (33.9% vs 16.1% p < 0.001) and candidosis (41.5% vs 22.3% p < 0.001). A greater number of HIV tests were also performed (19% vs 9% p < 0.01). Sixteen (12.4%) women were HIV positive. Their attendance record at both first appointment (88% vs 64% p < 0.05) and subsequent follow-up appointments (81% vs 43% p < 0.05) was significantly higher than a comparable group of women seen by the same doctor (FB) in the Kobler Centre. The women also saw the health adviser more frequently. Although the number of injecting drug users was small (eight), all women currently injecting drugs entered a detoxification programme., Conclusion: The WOC has become an established and popular service at St Stephen's. Women not previously using medical services are attending. The multidisciplinary nature of the clinic encourages a wider use of medical and paramedical services. Attendance record for HIV positive women has improved significantly. Whether these factors will lead to improved standards of sexual health will require a longer period of audit. Seventy-nine per cent of women indicated they would use a family planning service if available. An integrated family planning clinic was introduced after the audit period.