Hydrogen peroxide via thromboxane A2 receptors mediates myogenic response of small skeletal muscle veins in rats.

UNLABELLED: We aimed to test two hypotheses: (1) isolated small veins develop substantial myogenic tone in response to elevation of intraluminal pressure, (2) H2O2 contributes to the mediation of myogenic response via activation of arachidonic acid (AA) cascade and release constrictor prostaglandins. METHODS: Small veins were isolated from gracilis muscle of male rats, then cannulated. Changes of diameter to increases in intraluminal pressure, H2O2 and arachidonic acid in the presence and absence of various inhibitors were measured by videomicroscope and microangiometer. At the end of experiments the passive diameter were obtained in Ca2+ -free PSS solution. RESULTS: Isolated rat gracilis muscle small veins developed a substantial myogenic tone in response to increases in intraluminal pressure (1-12 mmHg). Calculated maximum myogenic tone was 70 ± 5% at 10 mmHg. Presence of catalase or indomethacin or SQ 29,548 reduced significantly the pressure-induced myogenic response. Also, H2O2 (10-9-10-5 M) and arachidonic acid (10-7-10-4 M) elicited concentration dependent constrictions, which were inhibited by the presence of indomethacin or SQ 29,548. CONCLUSION: We propose that both myogenic response and pressure-induced release of H2O2 play important roles in regulating the vasomotor function of venules both in physiological and pathological conditions.

OS085. Decreased maternal circulating PLGF is a significant predictor of length of pregnancy in women with hypertensive disorders of pregnancy.

INTRODUCTION: Diagnosis of the presence of disease and prediction of the rate of progression of disease in women with hypertensive disorders of pregnancy remains a clinical problem. Better methods are needed to determine the magnitude of risk to support patient counseling and clinical management. OBJECTIVES: To investigate whether the level of free PlGF is a significant predictor of length of pregnancy in women with hypertension. METHODS: In this case-control study a single sample was taken between the 22nd and 34th completed gestational weeks from 130 pregnant women with a final diagnosis of: pre-eclampsia (PE), HELLP-syndrome, superimposed pre-eclampsia (SIPE), chronic hypertension (CHT), gestational hypertension (GHT), and normal healthy pregnancy (Control). Plasma was analysed for PlGF using the Triage® PlGF assay (Alere, San Diego). A positive PlGF test was defined as below the 5th centile of normal healthy pregnancy. Hazard ratios for length-of-pregnancy were calculated for a positive PlGF test in a multivariate Cox proportional hazards model adjusting for two covariates, the gestational age at sample collection and a final diagnosis of proteinuric hypertension (PE, HELLP, and SIPE). RESULTS: Median PlGF concentration was significantly lower in women with hypertension than in controls. Women with proteinuric hypertension had the lowest levels of PlGF. A positive PlGF test predicted delivery before 35 weeks in 93.7% women, and delivery before 37 weeks in 90.5% women. A positive PlGF test was associated with a significantly higher risk of imminent delivery. PlGF was a significant and independent predictor of women destined to deliver early because of maternal or fetal complication (adjusted Hazard Ratio of 3.43, 95%CI of 1.97 to 5.98). CONCLUSION: A positive PlGF test is significant predictor of length of pregnancy, independent of other diagnostic criteria. PlGF has the potential to identify increased risk without the limitation of non-specificity which exists with other diagnostic parameters.

PP056. Placental growth factor is a better predictor of preterm birth than uterine or umbilical artery doppler in hypertensive disorders of pregnancy.

INTRODUCTION: Diagnosis of the presence of disease and prediction of the rate of progression of disease in women with hypertensive disorders of pregnancy remains a clinical problem. OBJECTIVES: Adequate placentation and placental development are important for normal pregnancy. We determined whether PlGF is a better predictor of delivery before 34+0 and 37+0 weeks than uterine artery and umbilical artery doppler. METHODS: One hundred and four women presenting before the completed 34th week of pregnancy with hypertensive disorders of pregnancy were enrolled into the study. Final diagnosis was chronic hypertension (N=24), gestational hypertension (N=21), pre-eclampsia (N=24), HELLP-syndrome (N=15), superimposed preeclampsia (N=20). Blood draw occurred before the 34th week of pregnancy at the time of investigation for expedited delivery or expectant management. Plasma was analysed for PlGF by the Alere Triage® PlGF assay using fluorescently-labelled monoclonal antibodies against PlGF. A positive PlGF test was defined as below the 5th centile of normal healthy pregnancy. RESULTS: Of the 104 pregnant women, the level of PlGF was abnormal in 23 of 24 (96%) women with IUGR, compared to 10 of 24 (42%) and 14 of 24 (58%) for uterine artery doppler and umbilical artery doppler, respectively. In the case of pre-eclampsia, the level of PlGF was abnormal in 50 of 59 (85%), compared to 15 of 59 (25%) and 25 of 56 (45%) for uterine artery doppler and umbilical artery doppler, respectively. Forty four (42%) women required medical delivery before 34+0 weeks gestation and 68 (65%) before 37+0 weeks gestation (see Table). PlGF detected a higher number of women requiring early delivery than doppler. CONCLUSION: The new Triage® PlGF test provides useful information to inform clinical decisions in pregnancy-associated hypertensive disorders, before the 34th completed gestational week.

Thromboxane A(2) contributes to the mediation of flow-induced responses of skeletal muscle venules: role of cyclooxygenases 1 and 2.

BACKGROUND: It has been shown that increases in intraluminal flow elicit dilation in venules, but the mediation of response is not yet clarified. We hypothesized that - in addition to nitric oxide (NO) and dilator prostaglandins (PGI(2)/ PGE(2)) - thromboxane A(2) (TxA(2)) contributes to the mediation of flow-induced responses of venules. METHODS AND RESULTS: Isolated rat gracilis muscle venules (259 +/- 11 microm at 10 mm Hg) dilated as a function of intraluminal flow, which was augmented in the presence of the TxA(2) receptor antagonist SQ 29,548 or the TxA(2) synthase inhibitor ozagrel. In the presence of SQ 29,548, indomethacin or Nomega-nitro-L-arginine methyl-ester decreased flow-induced dilations, whereas in their simultaneous presence dilations were abolished. The selective cyclooxygenase (COX) 1 inhibitor SC 560 reduced, whereas the selective COX-2 inhibitor NS 398 enhanced flow-induced dilations. Immunohistochemistry showed that both COX-1 and COX-2 are present in the wall of venules. CONCLUSION: In skeletal muscle venules, increases in intraluminal flow elicit production of constrictor TxA(2), in addition to the dilator NO and PGI(2)/PGE(2), with an overall effect of limited dilation. These mediators are likely to have important roles in the multiple feedback regulation of wall shear stress in venules during changes in blood flow velocity and/or viscosity.