PubMed Health⌕ Search

Biomedical subjects

M K McLaughlin

Publications and source records attributed to M K McLaughlin.

At least 19 recordsLinked to original sources
PubMed1998

Altered active but not passive properties of mesenteric resistance arteries from the vitamin E-deprived rat.

1 We tested the hypothesis that lowering antioxidant protection through dietary vitamin E deprivation would alter active and passive mechanical properties in resistance arteries of the rat. Specifically, we hypothesized that vascular tone in isolated mesenteric arteries of the vitamin E-deprived rats would be altered due to impaired endothelial influences of nitric oxide and/or prostaglandins. 2 Lumen diameter and wall thickness were measured in pressurized arteries (approximately 250 microm diameter) from control (n=9) and vitamin E deprived (n=9) Sprague-Dawley female rats by use of a dimension analysing system. 3 Treatment with a cyclo-oxygenase inhibitor (meclofenamate) did not affect the basal vascular tone in either group. Treatment with a nitric oxide synthase inhibitor (NG-methyl-L-arginine) caused a significant increase in basal tone only in the vitamin E-deprived rats (% tone: 6.2+/-1.1 vs 1.2+/-0.3%; P<0.05). When tone was induced to 25% of the initial diameter with phenylephrine, treatment with the nitric oxide synthase inhibitor resulted in a greater potentiated tone in the vitamin E-deprived rats compared to the controls (26.5+/-2.7 vs 16.4+/-3.4%; P<0.05); suggesting a greater nitric oxide affect in the vessels from the vitamin E-deprived rats. Meclofenamate treatment in the induced tone arteries significantly relaxed (-17.4+/-4.0%; P<0.05) only the arteries from the vitamin E-deprived rats, indicating that a vasoconstrictor was modifying tone. The passive characteristics of distensibility and stress-strain relationship were not different between the two groups of rats. 4 In summary, vitamin E deprivation in the rat enhanced the modulation of vascular tone by both the nitric oxide and cyclo-oxygenase pathways but did not alter passive characteristics of mesenteric arteries.

Animals↗
PubMed1998

Contribution of vasomotion to vascular resistance: a comparison of arteries from virgin and pregnant rats.

Intrinsic oscillatory activity, or vasomotion, within the microcirculation has many potential functions, including modulation of vascular resistance. Alterations in oscillatory activity during pregnancy may contribute to the marked reduction in vascular resistance. The purpose of this study was 1) to mathematically model the oscillatory changes in vessel diameter and determine the effect on vascular resistance and 2) to characterize the vasomotion in resistance arteries of pregnant and nonpregnant (virgin) rats. Mesenteric arteries were isolated from Sprague-Dawley rats and studied in a pressurized arteriograph. Mathematical modeling demonstrated that the resistance in a vessel with vasomotion was greater than that in a static vessel with the same mean radius. During constriction with the alpha1-adrenergic agonist phenylephrine, the amplitude of oscillation was less in the arteries from pregnant rats. We conclude that vasomotor activity may provide a mechanism to regulate vascular resistance and blood flow independent of static changes in arterial diameter. During pregnancy the decrease in vasomotor activity in resistance arteries may contribute to the reduction in peripheral vascular resistance.

Adrenergic alpha-Agonists↗
PubMed1998

Vascular function in the vitamin E-deprived rat: an interaction between nitric oxide and superoxide anions.

We tested the hypothesis that oxidative stress, mediated by dietary vitamin E deprivation, would alter vascular function through the interaction of oxygen-derived free radicals and nitric oxide (NO). This interaction may play an important role in the vascular pathophysiology of many diseases associated with oxidative stress. Mesenteric arteries from control (n = 12) and vitamin E-deprived (n = 12) Sprague-Dawley rats were studied with a myograph. Superoxide dismutase, which scavenges superoxide anions, produced a significantly greater relaxation in the arteries from the vitamin E-deprived rats compared with the controls (P<.05). Superoxide dismutase and catalase produced results similar to superoxide dismutase alone. Pretreatment with an NO synthase inhibitor eliminated the superoxide dismutase-induced relaxation in arteries from both control and vitamin E-deprived rats. L-Arginine induced a greater relaxation in arteries of the vitamin E-deprived group (P<.05). Agonist-induced relaxation with methacholine was not altered by superoxide dismutase for either group of animals, indicating that stimulated release of NO was not influenced by superoxide anions. With the use of Western immunoblot analysis, nitrotyrosine residues were shown to be present in arteries from both the vitamin E-deprived and control rats, but the amount of nitrotyrosine observed was not different between the two groups. In summary, our data indicate that there is a greater inhibition of NO caused by superoxide anions in the vitamin E-deprived group. We speculate that in conditions of oxidative stress (reduced vitamin E levels), altered vascular function may be due to increased destruction of NO by oxygen-derived free radicals.

Animals↗
PubMed1997

Increased ascorbate radical formation and ascorbate depletion in plasma from women with preeclampsia: implications for oxidative stress.

There is evidence that oxidative stress accompanies preeclampsia and plasma ascorbate concentrations are reported to be decreased in the disorder. We tested the hypothesis that an ascorbate-oxidizing activity is increased in plasma from women with preeclampsia relative to normal pregnancy. Electron paramagnetic resonance (EPR) spectroscopy was used to determine (1) plasma functional reserves of ascorbate and total thiols, (2) temporal changes in ascorbate and thiol concentrations during incubation of whole blood in vitro, and (3) ascorbate radical signal kinetics in plasma after equalization of ascorbate concentrations. High-pressure liquid chromatography (HPLC) was used to measure plasma alpha-tocopherol. Ascorbate concentrations were 50% lower in preeclampsia relative to normal pregnancy plasma but thiols and alpha-tocopherol did not differ. The elapsed time prior to half-consumption of plasma ascorbate was decreased approximately three-fold during incubation of whole blood from preeclamptics. No concomitant decrease in thiols was evident. The initial ascorbate radical signal amplitude was greater in preeclampsia plasma and then, in contrast to normal pregnancy plasma, decreased progressively. The iron chelator, deferoxamine had no effect on plasma ascorbate radical formation. We conclude that an ascorbate-oxidizing activity is increased in preeclampsia plasma which might contribute to vascular dysfunction in the disorder.

Adult↗
PubMed1997

Contribution of chondroitin-dermatan sulfate-containing proteoglycans to the function of rat mesenteric arteries.

Proteoglycans are an important nonfibrous matrix component of the arterial wall. Direct evidence for their role in resistance-sized arteries is lacking, although they likely have an important role in coordinating and regulating vessel behavior, presumably via interactions of their glycosaminoglycan chains or core proteins with other matrix molecules and/or the smooth muscle cell surface. The purpose of this study was to determine whether the removal of specific glycosaminoglycan chains from proteoglycans in resistance-sized mesenteric arteries would change the mechanical properties of the arterial wall, thereby affecting their functional behavior. The major finding of the study was that 65% removal of chondroitin-dermatan sulfate-containing glycosaminoglycans from the arterial wall increased vascular wall stiffness and altered the myogenic behavior of the artery. The significant alterations in myogenic behavior associated with changes in passive mechanics following partial glycosaminoglycan chain removal support our hypothesis that chondroitin-dermatan sulfate-containing proteoglycans contribute significantly to the functional behavior of resistance arteries. We speculate that these alterations are the result of changes in stress transfer between collagen fibrils and/or stress transfer between cells and collagen fibrils under applied pressure.

Animals↗
PubMed1997

Intrinsic tone and passive mechanics of isolated renal arteries from virgin and late-pregnant rats.

The purpose of this study was to investigate whether there are alterations in the intrinsic properties of renal interlobar arteries during pregnancy. Renal interlobar arteries (internal diameter approximately 250 microns) from virgin and late-pregnant rats were mounted in a pressurized arteriograph system. Intrinsic tone was quantified as the percent difference in luminal diameter of each artery in the presence of physiological saline solution and while pharmacologically relaxed with papaverine. At pressures between 75 and 125 mmHg, tone was 35-50% less in arteries from pregnant rats (P < 0.05). Endothelial removal reduced tone in arteries from virgin rats but had no effect on arteries from pregnant rats. Analysis of stress-strain curves (rate constants: pregnant, 6.31 +/- 0.38; virgin, 7.81 +/- 0.78; P < 0.05) indicate that there is a decrease in arterial stiffness in gestation. Thus pregnancy is associated with a reduced intrinsic tone, possibly because of a reduction in an endothelial constrictor influence on the vascular smooth muscle in isolated rat renal interlobar arteries. This effect, coupled with the decreased arterial stiffness, demonstrates the significant arterial adaptation occurring during pregnancy.

Animals↗
PubMed1996

Fasting serum triglycerides, free fatty acids, and malondialdehyde are increased in preeclampsia, are positively correlated, and decrease within 48 hours post partum.

OBJECTIVE: We tested the hypothesis that serum free (nonesterified) fatty acid and triglyceride concentrations are increased in nulliparous women with preeclampsia relative to women with uncomplicated pregnancies and that these lipids decrease post partum, consistent with the known resolution of clinical symptoms. The relationships between serum concentrations of these lipids and the lipid peroxidation metabolite malondialdehyde were also examined. STUDY DESIGN: Predelivery and 24 to 48 hour postpartum venous blood samples were collected from eight women with preeclampsia and nine women with uncomplicated pregnancies after an 8- to 10-hour fast. Sera were analyzed for concentrations of triglycerides, free fatty acids, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and malondialdehyde. RESULTS: Antepartum serum triglyceride and free fatty acid concentrations were increased approximately twofold in women with preeclampsia relative to uncomplicated pregnancies (p <0.02 and 0.004, respectively). Total, high-density lipoprotein, and low-density lipoprotein cholesterol concentrations did not differ between groups. Concentrations of all lipids decreased significantly in both groups within 48 hours post partum. However, triglyceride and free fatty acid concentrations remained higher in women with preeclampsia (p<0.006, both variables). Triglyceride and free fatty acid concentrations correlated positively, both ante partum (R2 0.42, p<0.01) and post partum (R2 0.39, p<0.02). Antepartum concentrations of malondialdehyde were 50% higher in women with preeclampsia (p<0.01) and decreased post partum (p <0.02) but did not decrease in controls (p = 0.07). Antepartum serum triglycerides and free fatty acids correlated positively with malondialdehyde concentrations (R2 0.38, p <0.02, both cases). CONCLUSION: Triglycerides and free fatty acids, but not cholesterol, are increased in preeclampsia and correlate with the lipid peroxidation metabolite malondialdehyde. We speculate that these interactions may contribute to endothelial cell dysfunction in preeclampsia.

Adult↗
PubMed1996

Decreased transferrin and increased transferrin saturation in sera of women with preeclampsia: implications for oxidative stress.

OBJECTIVE: The concerted iron-binding antioxidant activity of transferrin and ceruloplasmin decreases with increasing transferrin saturation by iron. We examined interactions between serum iron and iron-binding capacity and concentrations of the lipid peroxidation metabolite malondialdehyde in normal and preeclamptic pregnancies. We also asked if the release of iron from free hemoglobin by lipid hydroperoxides is a potential mechanism to increase transferrin saturation in preeclampsia. STUDY DESIGN: Predelivery and 24 to 48 hour postpartum venous blood was collected from 19 women with uncomplicated pregnancies and 17 with preeclampsia. Serum iron, iron binding capacity, and malondialdehyde were measured. In a subset of predelivery samples electron paramagnetic resonance spectroscopy was used to determine diferric transferrin, total transferrin, and ceruloplasmin concentrations and to examine interactions of an organic hydroperoxide with hemoglobin and transferrin. RESULTS: Antepartum serum iron concentrations were 46% greater, percent saturation of iron binding capacity was 98% greater, and malondialdehyde 50% greater, whereas total iron-binding capacity was 14% lower, in women with preeclampsia. By 48 hours post partum group differences between these variables other than total iron-binding capacity were not observed. Electron paramagnetic resonance spectroscopy confirmed antepartum differences and that total iron-binding capacity and percent saturation were equivalent to total transferrin and the ratio diferric transferrin/total transferrin, respectively. Antepartum concentrations of ceruloplasmin were not different. Antepartum malondialdehyde concentrations correlated positively with percent transferrin saturation and negatively with unsaturated iron-binding capacity (apotransferrin). Electron paramagnetic resonance spectroscopy demonstrated that the release of iron from free hemoglobin by lipid hydroperoxides in serum is a potential mechanism to increase transferrin saturation. CONCLUSION: Increased transferrin saturation and decreased unsaturated iron-binding capacity in preeclampsia may occur consequent to oxidative stress and then further promote oxidative stress by decreasing serum antioxidant buffering against redox-active iron.

Adult↗
PubMed1996

Impairment of vascular function is associated with an age-related increase of lipid peroxidation in rats.

We tested the hypothesis that an increase in endogenous lipid peroxidation over time is associated with an impairment of endothelium-dependent vascular function in resistance-sized mesenteric arteries that is due in part to alterations of arachidonate metabolism. Susceptibility to red blood cell hemolysis and sera levels of malondialdehyde were increased (P < 0.05) from 20 wk (n = 12) to 40 wk (n = 12) in female Sprague-Dawley rats. Arteries were studied in a myograph by examining the endothelial modification of phenylephrine vasoconstriction and the relaxation responses of the mesenteric arteries to methacholine. We observed the following. 1) An increase in sensitivity to alpha 1-adrenergic stimulation occurred between 20 and 40 wk of age. Cyclooxygenase inhibition decreased the sensitivity to phenylephrine only in the arteries from the 40-wk-old rats, indicating that a cyclooxygenase-dependent vasoconstrictor was modifying the phenylephrine response. 2) Nitric oxide synthase inhibition caused a greater increase in phenylephrine sensitivity in the arteries from the 20-wk-old rats than those from the 40-wk-old rats, indicating that nitric oxide modification of phenylephrine sensitivity decreased with age. 3) Endothelium-independent relaxations were not affected between 20 and 40 wk of age. 4) At 40 wk, the sensitivity to the methacholine-mediated relaxation response decreased without impairing the maximal relaxation response. This reduced sensitivity was removed with cyclooxygenase inhibition or thromboxane A2/prostaglandin H2 (PGH2) receptor blockade. 5) Aortas from the 40-wk-old rats had an increased expression of PGH synthase. Collectively, these observations indicate that, in the female rat, an increase in lipid peroxidation over time is associated with changes in endothelium-dependent vascular function that were due in part to a cyclooxygenase-dependent vasoconstrictor.

Aging↗
PubMed1995

Plasma from preeclamptic women increases human endothelial cell prostacyclin production without changes in cellular enzyme activity or mass.

OBJECTIVE: We investigated differences in prostacyclin production by endothelial cells exposed to plasma from either preeclamptic women or normal pregnant women. STUDY DESIGN: A case-control study of matched preeclamptic and normal pregnancies was used to compare prostacyclin synthesis by human umbilical vein endothelial cells incubated with pregnancy plasma for 24 hours. Prostacyclin concentrations in conditioned media were measured by radioimmunoassay of its stable metabolite (6-keto-prostaglandin F1 alpha). Human umbilical vein endothelial cell lysates were used to determine concentrations of the enzymes cyclooxygenase and prostacyclin synthase. RESULTS: Prostacyclin production by human umbilical vein endothelial cells incubated with plasma from preeclamptic women was significantly greater than that by cells exposed to normal pregnancy plasma. Differences in prostacyclin production under the two experimental conditions could be explained neither by differences in enzyme mass nor activities of cyclooxygenase and prostacyclin synthase. CONCLUSION: The stimulatory effect of preeclampsia plasma on prostacyclin biosynthesis in human umbilical vein endothelial cells appears to be manifested at a step(s) proximal to the activation of cyclooxygenase. Possible mechanisms are increased phospholipase A2, lipoprotein, or lipid peroxide activities in preeclampsia.

Case-Control Studies↗
PubMed1995

Nitric oxide biosynthesis during pregnancy: implications for circulatory changes.

1. The biosynthesis of NO and its second messenger, cGMP, increases from pre-pregnant levels during rat gestation. An increase in plasma level and urinary excretion of cGMP is also evident during human pregnancy. However, the relative contribution of the maternal vasculature and other tissues to increased NO and cGMP biosynthesis during gestation is uncertain. Consensus is lacking about the contribution of NO to reduced maternal vascular tone and reactivity during gestation in various organ beds; clearly, further investigation is still needed. That NO may also regulate vascular smooth muscle behaviour during pregnancy by altering membrane potential is another intriguing possibility. 2. The syncytiotrophoblast of the human placenta expresses significant NO synthase activity, and along with the fetoplacental endothelium undoubtedly contributes to NO production during pregnancy. 3. Finally, it should be emphasized that vascular studies in gravid animal models need to be extended to pregnant women.

Animals↗
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

Characteristics of vascular smooth muscle in the maternal resistance circulation during pregnancy in the rat.

OBJECTIVE: Our purpose was to determine if pregnancy results in a decrease in arterial sensitivity to receptor-independent stimuli and a change in vascular smooth muscle membrane potential. STUDY DESIGN: Mesenteric resistance arteries from late pregnant (n = 19) and age-matched virgin control (n = 20) Sprague-Dawley rats were studied in a pressurized arteriograph system or isometric myograph. RESULTS: Arteries from pregnant rats were less sensitive to membrane depolarization by K+ than were those from nonpregnant rats (mean effective concentration that produced a 50% response 49 vs 39 mmol/L, pregnant vs nonpregnant, p < 0.05). Arterial basal tone and the myogenic response to increasing pressure steps were also reduced in arteries from pregnant rats compared with nonpregnant controls. The vascular smooth muscle membrane of the arteries from the pregnant rats was hyperpolarized compared with that from the control rats (-64 mV from pregnant rats vs -57 mV from nonpregnant rats, p < 0.01). This was associated with a reduction in vasomotion in the arteries from the pregnant rats (10% for pregnant rats vs 45% from nonpregnant rats, p < 0.01). CONCLUSION: Pregnancy results in alterations of the vascular smooth muscle, including changes in the regulation of membrane potential and a reduced sensitivity to receptor-independent stimuli.

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

Changes in sodium transport during the human menstrual cycle and pregnancy.

1. We have studied the transport of Na+ and K+ by erythrocytes during the follicular and luteal phases of the human menstrual cycle, and in pregnant compared with non-pregnant women. Venous blood was drawn from 10 healthy young women (not taking any medication or hormones) 1-2 days after menstruation and from the same women 7-9 days after ovulation. For the pregnancy part of the study, blood was drawn from eight other normotensive non-pregnant women and from eight age-matched normotensive pregnant women (36-43 weeks gestation). 2. Intracellular erythrocyte and plasma Na+ and K+ concentrations were measured by flame photometry. The increase in the intracellular Na+ concentration during a 1 h 37 degrees C incubation of fresh whole blood with 0.2 mmol/l ouabain (compared with no ouabain) was measured to determine the rate of active Na+ efflux. The Na(+)-K+ pump rate constant was calculated by dividing the active Na+ efflux rate by the intracellular Na+ concentration. 3. In fresh blood, the intracellular erythrocyte Na+ concentration (P < 0.002) and the plasma K+ concentration (P < 0.01) were both lower in pregnant than in non-pregnant women. The Na(+)-K+ pump rate constant was higher (P < 0.02) during the luteal phase than during the follicular phase, and in pregnant compared with non-pregnant women. 4. We conclude that short-acting hormones in the plasma most probably account for the changes in the Na(+)-K+ pump rate constant during the menstrual cycle.

Adult↗