Biomedical subjects

S T Davidge

Publications and source records attributed to S T Davidge.

64 records · Page 4Linked to original sources

PubMed1994

Lipid peroxidation increases arterial cyclooxygenase activity during pregnancy.

OBJECTIVE: We tested the hypothesis that increased production of lipid peroxides (induced by a mild vitamin E deficiency) during pregnancy would alter the cyclooxygenase pathway of arachidonate metabolism, resulting in impaired endothelial-dependent vascular function. STUDY DESIGN: Mesenteric arteries from pregnant control (n = 12) and pregnant vitamin E-deprived (n = 12) Sprague-Dawley rats were studied in a myograph. RESULTS: Surprisingly, endothelial-dependent relaxations to methacholine were enhanced in arteries from the pregnant vitamin E-deprived rats compared with the pregnant control rats (mean effective concentration producing a 50% response = 0.034 vs 0.046 mumol/L, p < 0.05). In the arteries from the vitamin E-deprived rats this enhanced response was blunted and the group difference eliminated in the presence of a cyclooxygenase inhibitor (1 mumol/L meclofenamate, mean effective concentration producing a 50% response 0.057 vs 0.034 mumol/L, p < 0.05) but had no effect on the arteries from the control pregnant rats. The thromboxane A2-prostaglandin H2 receptor blocker (1 mumol/L SQ 29548) had no effect on the arteries from either group. Endothelial-independent relaxations to sodium nitroprusside were not affected by vitamin E deprivation. Arachidonic acid elicited less tension in the arteries from the vitamin E-deprived rats compared with the controls (at 10 mumol/L: 0.41 vs 0.90 mN/mm, p < 0.01). Cyclooxygenase inhibition potentiated the vasoconstrictor response only in the arteries from the vitamin E-deprived rats (at 10 mumol/L: 0.92 vs 0.41 mN/mm, p < 0.01) so that the group difference was eliminated. CONCLUSION: An elevation of lipid peroxides, mediated by a mild vitamin E deprivation, resulted in an increased cyclooxygenase-dependent vasorelaxation in the mesenteric arteries of the pregnant rat.

Animals↗

PubMed1993

Pregnancy and lipid peroxide-induced alterations of eicosanoid-metabolizing enzymes in the aorta of the rat.

OBJECTIVES: We examined whether pregnancy modulates the expression of prostaglandin endoperoxide synthase, prostacyclin synthase, and thromboxane A2 synthase in the systemic vasculature. Further, we examined whether elevated lipid peroxidation during pregnancy (induced by vitamin E deprivation) affects the normal adaptive process to pregnancy. STUDY DESIGN: Western immunoblotting was performed on aortas from normal and vitamin E-deprived late pregnant (18 to 19 days) and age-matched virgin control rats. RESULTS: Normal pregnancy resulted in an increased expression of prostaglandin endoperoxide synthase (2.91 vs 1.06 fmol/ng deoxyribonucleic acid, p < 0.05). Surprisingly, the expression for both prostacyclin and thromboxane A2 synthases were significantly decreased by pregnancy: prostacyclin synthase 2.60 versus 13.82 units/ng deoxyribonucleic acid and thromboxane A2 synthase 1.32 versus 9.85 units/ng of deoxyribonucleic acid. Elevation of endogenous lipid peroxidation partially reversed this normal pregnancy trend in enzyme expression: prostaglandin endoperoxide synthase 1.85 fmol/ng deoxyribonucleic acid, prostacyclin synthase 9.38 units/ng deoxyribonucleic acid, thromboxane A2 synthase 4.36 units/ng deoxyribonucleic acid. CONCLUSION: Changes in prostanoid activity in the systemic vasculature during pregnancy may be mediated by concerted induction and down-regulation of specific enzymes. Increased lipid peroxidation interferes with this normal pregnant pattern. Further studies on the cell-specific expression of these genes will help to define the cardiovascular role of prostaglandins in pregnancy and in preeclampsia.

Animals↗

PubMed1993

Lipid hydroperoxides potentiate mesenteric artery vasoconstrictor responses.

The aim of this study was to investigate the effects of lipid and organic hydroperoxides on vasomotor activity of isolated rat superior mesenteric arteries. Hydroperoxides did not elicit measurable responses in unstimulated (quiescent) mesenteric arteries. Contractile responses to potassium, however, were significantly potentiated by 13-(s)-hydroperoxylinoleic acid (range 3-54 microM). Potentiation of potassium responses by linoleic acid (18:2) and linolenic acid (18:3) was increased by pretreatment of the fatty acids with lipoxygenase (p < .01). Lipoxygenase alone had no contractile effects. Lipoxygenase-treated 18:2, tert-butyl hydroperoxide, and hydrogen peroxide augmented contractile responses to phenylephrine, but to a lesser degree than corresponding augmentation of potassium responses. Contractile responses to lipoxygenase-treated 18:3 were blunted by vitamin E (p < .02) and by nitroblue tetrazolium (p < .02), whereas catalase and mannitol had no effects, implicating lipid free radicals in the contractile response. Responses to lipid hydroperoxides were not significantly altered by prostaglandin inhibitors. Endothelial cell denudation significantly enhanced the contractile responses elicited by 13-(s)-hydroperoxylinoleic acid (p < .05), indicating that lipid hydroperoxides enhance agonist-induced contractions by a direct effect on the smooth muscle. These results support a hypothesized link between lipid peroxidation and development of altered vascular function. They further suggest that the vascular endothelium may play an important role in regulation of vasomotor responses to lipid hydroperoxides.

Animals↗

PubMed1993

Cyclooxygenase-dependent vasoconstrictor alters vascular function in the vitamin E-deprived rat.

We tested the hypothesis that increased production of lipid peroxides, mediated by a dietary vitamin E deprivation, would alter the cyclooxygenase pathway of arachidonate metabolism, resulting in impaired endothelium-dependent vascular function. Mesenteric arteries from control (n = 12) and vitamin E-deprived (n = 12) Sprague-Dawley rats were studied in a myograph. Endothelium-dependent relaxations to methacholine were similar in the arteries from vitamin E-deprived rats compared with control arteries (EC50, 0.057 +/- 0.006 versus 0.065 +/- 0.009 microM). However, in the arteries from the vitamin E-deprived rats, this response was potentiated in the presence of a cyclooxygenase inhibitor (1 microM meclofenamate; EC50, 0.035 +/- 0.003 versus 0.057 +/- 0.006 microM; P < .05) or thromboxane A2/prostaglandin H2 receptor blocker (1 microM SQ 29548; EC50 0.029 +/- 0.002 versus 0.057 +/- 0.006 microM; P < .05) but had no effect on the arteries from the control rats. Endothelium-independent relaxations to sodium nitroprusside were not effected by vitamin E deprivation. Arachidonic acid increased tension twofold more in the arteries from the vitamin E-deprived rats compared with the control rats (at 1 microM; 0.43 +/- 0.05 versus 0.23 +/- 0.03 mN/mm; P < .05). The enhanced vasoconstriction was blunted, and the group difference was eliminated by a cyclooxygenase inhibitor (0.15 +/- 0.02 versus 0.43 +/- 0.05 mN/mm, P < .05) or a thromboxane A2/prostaglandin H2 receptor blocker (0.17 +/- 0.04 versus 0.43 +/- 0.05 mN/mm, P < .05). Prostaglandin endoperoxide synthase expression, determined by Western immunoblotting on aortas from the same rats, was increased in the vitamin E-deprived rats (3.14 +/- 0.8 versus 1.06 +/- 0.4 fmol/ng DNA, P < .05). In summary, mesenteric arteries from the vitamin E-deprived rats demonstrated altered endothelium-dependent responses that were in part due to a cyclooxygenase-dependent vasoconstrictor binding to the thromboxane A2/prostaglandin H2 receptor. In the aorta, there was an associative increase in the expression of prostaglandin endoperoxide synthase. We speculate that, in some vascular diseases, increased lipid peroxidation may influence endothelium-dependent vascular function by modulating the cyclooxygenase pathway of arachidonate metabolism.

Animals↗

PubMed1992

Endogenous modulation of the blunted adrenergic response in resistance-sized mesenteric arteries from the pregnant rat.

OBJECTIVE: We tested the hypothesis that during pregnancy the endothelium mediates the blunted response to adrenergic vasoconstriction. STUDY DESIGN: Mesenteric resistance arteries from late pregnant (n = 6) and age-matched virgin control (n = 6) Sprague-Dawley rats were studied in a myograph. RESULTS: Arteries from pregnant rats were 35% less sensitive to phenylephrine vasoconstriction than were those from nonpregnant rats (mean effective concentration that produced a 50% response 2.26 vs 1.48 mumol/L, pregnant vs nonpregnant, p < 0.01). Meclofenamate had no effect on the vasoconstrictor response in arteries from either group. Inhibition of endothelium-derived relaxing factor with N(o)-nitro-L-arginine methyl ester or endothelial cell removal had a similar twofold increase in phenylephrine sensitivity in arteries from both the pregnant and nonpregnant rats (mean effective concentration that produced a 50% response 2.26 vs 1.11 mumol/L for pregnant rats and 1.48 vs 0.72 mumol/L for nonpregnant rats, p < 0.01). However, methacholine relaxation response was potentiated in pregnant versus nonpregnant rats (mean effective concentration that produced a 50% response 0.030 vs 0.049 mumol/L, p < 0.01). CONCLUSION: Although the potential for endothelium-dependent relaxation is augmented in mesenteric arteries of the pregnant rat, the decreased sensitivity to phenylephrine during pregnancy is not modulated acutely by endothelium-derived relaxing factor or by prostaglandin products of the cyclooxygenase pathway.

Animals↗

PubMed1992

Sera antioxidant activity in uncomplicated and preeclamptic pregnancies.

Uncontrolled lipid peroxidation may play an important role in the pathophysiology of preeclampsia by causing vascular endothelial cell dysfunction. Sera contain antioxidant mechanisms that serve to control lipid peroxidation. We tested the hypothesis that the sera antioxidant protective mechanisms are diminished in women with preeclampsia. Blood samples were collected within 24 hours of delivery (pre-delivery) and by 24 hours postpartum (post-delivery) from women with preeclampsia (N = 8) and from matched controls with uncomplicated pregnancies (N = 8). Antioxidant activity was determined by the ability of sera to inhibit autoxidation of a standardized brain homogenate. Lipid peroxidation of both brain homogenate and sera was analyzed by high-pressure liquid chromatography using the amount of malondialdehyde present as an indicator of peroxidation. Pre-delivery sera from women with preeclamptic pregnancies had one-half the antioxidant activity of sera from women with uncomplicated pregnancies (42 versus 90%; P less than .01). Malondialdehyde values alone were not significantly different between the groups in either the pre-delivery or post-delivery samples. When using a ratio to evaluate the relative balance between lipid peroxidation and antioxidant activity, pre-delivery samples from women with preeclampsia had over a twofold increase in this ratio compared with samples from uncomplicated pregnancies. In conclusion, in contrast to women with uncomplicated pregnancies, women with preeclampsia have antioxidant activity that is markedly reduced by late gestation. For women with preeclampsia, this may result in a greater potential for endothelial oxidative damage.

Adolescent↗

PubMed1988

Influence of cornual insemination on conception in dairy cattle.

The objective of this study was to compare conception to artificial insemination (AI) services in dairy cattle when semen was deposited into the uterine body or into both uterine horns (cornual insemination). Nine herdsman inseminators (HI) in four commercial dairy herds in Washington constituted the experimental units. Herds ranged in size from 393 cows to 964 cows. The duration of the experiment was 12 mo in three herds and 18 mo in the fourth herd. At the beginning of the experiment all inseminators were trained to deposit semen in the body of the uterus. Inseminators were instructed to use this method for 6 mo. Following employment of body deposition, the same inseminators were retrained to deposit one-half of the semen into the right uterine horn and one-half into the left uterine horn. Cornual inseminations were performed for 6 mo. A total of 4,178 services constituted the data set. Milk samples were collected from cows on the day of insemination and later were assayed for progesterone (P4). There was variation (P less than .01) in conception associated with month of insemination and insemination method (P less than .001). The monthly variation was not associated with season of the year. Least squares means for conception when semen was deposited in the uterine body was 44.7%, compared with 64.6% when cornual insemination was employed. The insemination treatment X inseminator interaction was not significant. Results suggest that cornual insemination provides an alternative to deposition of semen in the uterine body.

Animal Husbandry↗

PubMed1987

Influence of varying levels of blood progesterone upon estrous behavior in cattle.

The effect of four levels of progesterone on the occurrence and intensity of estrous behavior was determined in ovariectomized cows. Twelve Holsteins were bilaterally ovariectomized at least 2 mo before treatment. Progesterone (P4) was administered im two times/day for 5 d followed 72 h later with 2 mg estradiol (E2) im to induce estrous behavior. Treatments were control = oil, 100 mg P4/d, 300 mg P4/d and 500 mg P4/d. Each animal received all P4 treatments in a 4 X 4 Latin-square design. From d 2 through 6, with d 1 being the first day of P4 treatment, serum P4 concentrations averaged .3, 2.5, 6.1 and 12.3 ng/ml in treatments I to IV, respectively. Progesterone levels at the time of peak E2 (d9) were less than 1 ng/ml for treatments I, II and III and 1.8 ng/ml for treatment IV. Peak E2 levels for all groups averaged 23.9 pg/ml (12 h after E2 injection). Cows were observed continuously for 48 h after E2 injection to quantitate estrous behavior. Behavioral traits measured were: mounts initiated, mounts received, standing when mounted, chin rests initiated and chin rests received. Progesterone treatment caused a decrease in frequency of all five traits measured. As P4 levels increased, there was a linear (P less than .01) decrease in frequency of a behavioral trait. The percentage of the cows that showed each behavioral trait and mean time to first occurrence of each trait were not different after progesterone treatment, with the exception of standing behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Effect of oxygen levels in villous trophoblast apoptosis.

In pregnancies complicated by intrauterine growth restriction (IUGR), the villous trophoblast shows increased apoptosis and immature cytotrophoblasts (CT) may be exposed to both higher or lower oxygen levels than normal placentae. We propose that villous CT undergo higher frequencies of apoptosis at extreme oxygen tensions. The apoptosis of CT isolated from normal term placentae was examined before culture and after 24 h of culture at different oxygen tensions with or without TNFalpha. The apoptosis frequencies of cells cultured for 24 h at O2 levels of approximately 15 mm and approximately 38 mm Hg were similar to the frequency before culture. Both constitutive and TNFalpha-induced apoptosis and cell loss were highest at low (<10 mm Hg) and high ( approximately 140 mm Hg) oxygen tensions. Further, the ratios of induced to constitutive apoptosis, constant from approximately 15 mm to approximately 140 mm Hg, indicate induced apoptosis to be rather insensitive to changes in oxygen levels. These results show that primary villous trophoblasts from normal placentae undergo minimal apoptosis unless subjected to extreme oxygen tensions <15 mm or 140 mm Hg. The results indicate that normal villous trophoblasts are remarkably resistant to hypoxia-induced apoptosis.

Apoptosis↗

PubMedDate not supplied

Estrogen decreases prostaglandin H synthase products from endothelial cells.

OBJECTIVE: Because we showed recently that estrogen replacement prevents prostaglandin H synthase (PGHS)-dependent vasoconstriction in rats, the aim of this study was to determine how estradiol affects production of PGHS-dependent eicosanoids. METHODS: Cultured bovine coronary microvascular endothelial cells were exposed to physiologic levels of 17 beta-estradiol (0.01 nM [about 2.7 pg/mL], 0.1 nM [about 27 pg/mL], or 1.0 nM [about 270 pg/mL]) for 4, 8, or 24 hours. Thromboxane (TXA2), prostacyclin (PGI2), and nitric oxide (NO) were measured as their stable metabolites, thromboxane B2 (TXB2), 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha), and nitrite (NO2), respectively. RESULTS: Estradiol had no effect on nitrite production. However, exposure to 0.1 nM and 1.0 nM estradiol for 24 hours reduced TXB2 production to 67 +/- 16% and 69 +/- 12% of control, respectively. Furthermore, 0.1 nM and 1.0 nM estradiol also reduced production of 6-keto PGF1 alpha to 35 +/- 19% and 17 +/- 11% of control, respectively. Prostaglandin H synthase expression was not altered by estradiol. However, the estrogen receptor inhibitor, tamoxifen, reversed the inhibitory effect of estradiol. CONCLUSION: Estradiol acts through a receptor-dependent process to decrease PGHS-dependent products, thus further elucidating this novel effect of estradiol on the vascular system.

6-Ketoprostaglandin F1 alpha↗