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Biomedical subjects

M K McLaughlin

Publications and source records attributed to M K McLaughlin.

At least 55 records · Page 3Linked to original sources
PubMed1989

Vascular catecholamine sensitivity during pregnancy in the ewe.

Four pregnant and four castrated ewes were chronically instrumented for the measurement of external iliac blood flow to test the hypothesis that pregnancy alters alpha-adrenergic sensitivity in a major regional circulation. Complete dose-response curves were generated to methoxamine, phenylephrine, and norepinephrine. Pregnancy was associated with no change in methoxamine sensitivity, an increase in phenylephrine sensitivity, and a decrease in norepinephrine sensitivity. These differential changes in drug sensitivity suggest (1) the alpha 1-receptor population is functionally similar between the two groups of animals, (2) uptake 1 is inhibited, and (3) either catechol-O-methyltransferase activity is increased or the alpha 2- or beta-receptor population changes in this circulation during pregnancy. These data illustrate the complexity of the change in the adrenergic system during pregnancy.

Animals↗
PubMed1989

Preeclampsia: an endothelial cell disorder.

Despite intense study preeclampsia remains enigmatic and a major cause of maternal and fetal morbidity and mortality. Most investigative efforts have focused on the hypertensive component of this disorder with reduced attention given to other equally important characteristics. Increased sensitivity to pressor agents and activation of the coagulation cascade occur early in the course of preeclampsia, often antedating clinically recognizable disease. Inasmuch as endothelial cell injury reduces the synthesis of vasorelaxing agents, increases the production of vasoconstrictors, impairs synthesis of endogenous anticoagulants, and increases procoagulant production, these cells are likely to be implicated in the pathophysiology of preeclampsia. Indeed, evidence of endothelial cell injury is provided by the most characteristic morphologic lesion of preeclampsia, glomerular endotheliosis. Additional support for this hypothesis is derived from reports that indicate increased levels of circulating fibronectin (which can be released from injured endothelial cells) and increased factor VIII antigen present in the blood of preeclamptic women. More recently, direct evidence of activities that injure endothelial cells in vitro and increase the contractile sensitivity of isolated vessels has been presented. We propose that poorly perfused placental tissue releases a factor(s) into the systemic circulation that injuries endothelial cells. The changes initiated by endothelial cell injury set in motion a dysfunctional cascade of coagulation, vasoconstriction, and intravascular fluid redistribution that results in the clinical syndrome of preeclampsia.

Endothelium, Vascular↗
PubMed1989

Lipid peroxidation in pregnancy: new perspectives on preeclampsia.

Basic research during the past two decades has led to increased awareness of the role of lipid peroxidation in various physiologic and pathophysiologic processes. A number of reports indicate that preeclampsia is associated with elevated blood levels of lipid peroxidation products. In view of its potentially destructive character, uncontrolled lipid peroxidation has been suggested as an etiologic factor in preeclampsia. The present article summarizes current information regarding the occurrence of lipid peroxidation in normal and preeclamptic pregnancy. Recent progress concerning our understanding of the process of lipid peroxidation and its role in cardiovascular disease is also reviewed. This information is used to discuss potential mechanisms by which lipid peroxidation might contribute to the pathogenesis of preeclampsia.

Female↗
PubMed1989

Lipid peroxidation and altered vascular function in vitamin E-deficient rats.

Female rats deprived of dietary vitamin E for 35 wk postweaning were analyzed for changes in vascular function. A functional state of vitamin E deficiency was indicated by a marked increase in spontaneous hemolysis of washed red cells by 22 wk of feeding. Elevated thiobarbituric acid-reactive material in aorta, liver, and plasma samples from vitamin-E deficient rats indicated increased lipid hydroperoxide formation. Systolic blood pressures and heart rates measured biweekly were unaltered by diet. Before being killed, the rats were catheterized and allowed to recover from anesthesia (methohexital sodium ip). The pressor response to graded doses of angiotensin II was significantly increased in the vitamin E-deficient group relative to its control. Isolated superior mesenteric artery segments from vitamin E-deficient rats demonstrated significantly decreased relaxation responses to acetylcholine. In contrast, artery contractile responses to 50 mM potassium and to graded doses of extracellular calcium did not differ, indicating that contractile capability was maintained. Surface blebbing of the femoral artery endothelium was observed by scanning electron microscopy. These data support a proposed link between lipid peroxidation and development of altered vascular function.

Acetylcholine↗
PubMed1988

Ovine placental perfusion balance: effect of marijuana smoke.

This study was designed to test the hypothesis that maternal marijuana smoking impairs placental oxygen transfer in late ovine pregnancy by disrupting perfusion balance between the maternal and fetal placental circulations. Placental hemodynamics were assessed in nine chronically prepared ewes 1 hour after exposure to smoke from either a marijuana (n = 5) or a placebo (n = 4) cigarette. When compared with placebo smoke, maternal marijuana smoke exposure resulted in a fall in both uterine and umbilical placental vascular resistance and a 30% improvement in placental perfusion balance at a cotyledonary level. We conclude that maternal marijuana smoking in late ovine pregnancy has a direct relaxant effect on both maternal and fetal placental vascular smooth muscles that decreases the normal heterogeneity of flow and improves macroscopic placental perfusion balance. However, the observed concurrent 6 torr decrease in fetal oxygen tension suggests that perfusion balance is actually disrupted at a microcirculatory level.

Animals↗
PubMed1986

Pregnancy-induced changes in resistance blood vessels.

This study was designed to examine the effect of reproductive status on the basic mechanical properties of resistance size blood vessels. The hypothesis to be tested was that pregnancy is associated with alterations in both the passive and active properties of blood vessels small enough to be major determinants of peripheral vasculature resistance. Third-order arteries (165 microns in diameter) from the mesenteric arcade of the rat were removed at all three stages of gestation and the four stages of the estrous cycle. These were placed in a specially designed myograph system in which their active and passive tension-internal circumference characteristics were measured. Pregnancy was found to be associated with a decrease in stiffness of these vessels and a reduction in contractile ability by 20 days' gestation.

Animals↗
PubMed1985

Vascular reactivity in the hind limb of the pregnant ewe.

The data generated by this study are consistent with the fact that pregnancy and progesterone treatment are associated with an increase in vascular reactivity to phenylephrine and a decrease in reactivity to angiotensin II in the circulation to the hind limb of the ewe. This shows that the way in which vascular reactivity changes during pregnancy is dependent both upon the circulation and the vasoconstrictor being examined. It suggests that sensitivity and contractility could change in opposite directions in this circulation during pregnancy. This will require additional verification, both as to its existence and whether this is an important normal cardiovascular adaptation to pregnancy.

Angiotensin II↗
PubMed1985

An examination of vascular reactivity during pregnancy in the chronic ewe model.

The hind limb vascular responses to angiotensin II and phenylephrine, an alpha-adrenergic agonist, were determined in chronically instrumented pregnant (n = 7) and castrated (n = 6) ewes. On any one day, five doses of one or the other drug were administered directly into the arterial femoral circulation while the perfusion pressure and external iliac blood flow were monitored. The steady-state resistance change (baseline resistance - the resistance calculated during the 3 to 5 minutes of drug infusion) showed a reduction in vascular response to angiotensin II in the pregnant ewes compared to the controls, with no significant differences in response to phenylephrine. When the dynamic (within 40 seconds) rather than the steady-state changes were analyzed, a hyperreactivity to phenylephrine was present in the pregnant animals. These data are an illustration of the complex interactions that are present in the whole-body pressor responses to vasoactive stimuli during pregnancy.

Angiotensin II↗
PubMed1984

Regional distribution of cerebral blood flow in experimental intrauterine growth retardation.

The regional distribution of cerebral blood flow was assessed in eight control and eight morphometrically growth-retarded fetal lambs to determine whether perfusion patterns within the cerebral circulation are altered in this model of intrauterine growth retardation. Growth retardation was induced by repetitive embolization of the uterine circulation, and flow distribution was assessed by use of microspheres. Distribution to 22 separate areas, expressed as a flow/weight ratio, was virtually identical in the two groups. Cortical gray matter received 56% of total cerebral flow, and cortical white matter received 7%. However, flow X gm-1 in cortical white matter was 85% of that in cortical gray matter. We conclude that perfusion patterns within the cerebral circulation are not altered in this model of intrauterine growth retardation and that, compared to gray matter, cortical white matter has a high flow X gm-1 in fetal life.

Animals↗
PubMed1983

Differential sensitivity to angiotensin II in pregnant rabbits.

Threshold concentrations for angiotensin II and barium chloride were determined in the perfused hind limb of the nonpregnant, pseudopregnant, and pregnant rabbit. The threshold concentration for these vasoconstrictors was defined as the amount of drug per milliliter of hind limb blood flow which would increase hind limb blood pressure by 4 mm Hg. There was no difference in the mean angiotensin II threshold concentration between the nonpregnant and pseudopregnant rabbits. The angiotensin II dose for the pregnant rabbits was double that of the first two groups. There was no significant difference in the mean barium chloride threshold concentration between the three groups. This difference in the pregnant angiotensin II threshold concentration with no difference in barium chloride threshold concentration indicates a change in vascular sensitivity which is dependent upon a specific angiotensin II-receptor interaction and is not inherent in the contractile response of the vessel, nor is it mimicked by pseudopregnancy.

Angiotensin II↗
PubMed1982

The uterine hemodynamic response to repetitive unilateral vascular embolization in the pregnant ewe.

The longitudinal hemodynamic response of the uterine circulation to pregnancy and to repetitive embolic insult was assessed in 23 singleton ewe pregnancies by means of electromagnetic flow transducers and radionuclide-labeled microspheres. The data indicate that the longitudinal hemodynamic changes observed in the uterine circulation were directly related to the growth rate of the tissue which it supplied. The hemodynamic impact of embolization appears to be secondary to its impact on tissue growth. Embolization simply blunts the normal incremental increases in uterine perfusion and the cross-sectional area of the uterine vascular bed. It alters actual tissue perfusion only within a portion of the cotyledonary circulation. Finally, the data support the presence of functional arterial anastomoses between the two sides of the uterine circulation in this species.

Animals↗
PubMed1982

Ovine placental cortisol production.

Cortisol levels were determined by radioimmunoassay in samples simultaneously obtained from the four vessels serving the ovine placenta (uterine artery and vein, umbilical artery and vein). These samples were collected daily over a 20- to 30-day interval in three animals in the latter third of pregnancy. Cortisol levels in the uterine and umbilical veins were higher than those in the arteries in 67 of 73 sample sets. Net synthesis of 11-deoxycortisol and cortisol from 17 alpha-hydroxyprogesterone by dispersed placental cells was also demonstrated in vitro. These data provide strong evidence that the ovine placenta has the ability to synthesize 11-deoxycortisol and cortisol in vitro and normally does so in vivo.

Animals↗
PubMed1982

Identification and ontogenesis of beta-adrenergic receptors in fetal and neonatal rabbit myocardium.

In adult animals, beta-adrenergic receptors are involved in the regulation of myocardial contractility and heart rate. Their properties in the fetal and early neonatal period have not been adequately investigated. We have directly characterized beta-adrenergic receptors in rabbit fetal and neonatal myocardial membranes by a radioligand binding assay utilizing 125I-hydroxybenzylpindolol (I-HYP), a potent, non-specific, beta-adrenergic antagonist, I-HYP binding sites were detected as early as the 21st day of gestation (term 31 days). The binding was rapid, saturable and reversible. The dissociation constant, KD, as determined by Scatchard plots, ranged from 30 pM to 50 pM. There was a progressive increase in the density of the receptor sites with advancing gestation. Competition studies with beta-agonists and antagonists showed that the order of potency in inhibiting I-HYP binding was consistent with a beta 1-subtype of beta-adrenergic receptors. We conclude that the progressive increase in density of beta-adrenergic receptors in rabbit fetal myocardium parallels similar maturational processes occurring in other tissues with advancing gestation. It may also account for the reported developmental changes in fetal myocardial contractility.

Animals↗
PubMed1980

Effect of alpha-adrenergic agonist and antagonist infusion on the umbilical and uterine circulations of pregnant sheep.

The effects of the alpha-adrenergic agonists, norepinephrine and methoxamine, and the alpha-antagonist, phenoxybenzamine, on umbilical and uterine blood flows, fetal and maternal heart rates, arterial and venous pressures were examined in near-term chronic sheep preparations. Norepinephrine injection or methoxamine infusion to either fetus or ewe resulted n a respective unilateral fetal or maternal pressur response associated with bradycardial. Uterine blood flow decreased significantly with alpha-agonist administration to either fetus or ewe. Umbilical blood flow did not change with either, but an increase in calculated umbilicalo vascular resistance did occur after fetal administrations of the alpha-agonist. Thus, both the uterine and umbilical vascular beds are responsive to alpha-agonism, but maternal uteroplacental perfusion appears to be more sensitive. alpha-Blockade in either fetus or mother produced no significant changes in umbilical or uterine blood flows or fetal or maternal perfusion pressure suggesting that basal alpha-adrenergic tone is unnecessary for normal maintenance of either fetal or maternal uteroplacental circulation.

Adrenergic alpha-Agonists↗
PubMed1980

The effect of SAR1ALA8 AII on ovine uterine and umbilical blood flow.

The effects of Sar1Ala8 AII (Saralasin), an angiotensin II (AII) receptor blocker, were examined in the late gestation ewe and fetus. Maternal administration of Saralasin resulted in a reduction in both mean maternal systemic arterial pressure and uterine blood flow. There were no changes in the measured fetal indices during maternal drug administration. Infusion of Saralasin to the fetus caused variable reductions in mean fetal arterial blood pressure and umbilical flow. There were no changes in maternal parameters measured. Therefore, in pregnant sheep in the third trimester, a component of normal uterine blood flow is maintained by endogenous AII, primarily through maintenance of adequate perfusion pressure.

Angiotensin II↗
PubMed1980

Vascular response of the fetal placenta to local occlusion of the maternal placental vasculature.

Local regulation of fetal placental blood flow was studied in 6 near-term sheep. Maternal blood flow was reduced or eliminated to 6-17% of the placenta by ligation or embolization with non-radioactive microspheres. Maternal and fetal placental blood flows were measured, using radioactively-labelled microspheres, before and after vascular occlusion. The change in fetal placental blood flow was significantly different in the occluded as compared to the non-occluded cotyledons. Occlusion of the maternal placental vasculature was associated with a 40% decline in the adjacent fetal placental flow after 24 h. These data support the concept of a local regulatory interaction between fetal and maternal placental circulations wherein fetal placental blood flow is dependent upon the adjacent maternal flow.

Animals↗