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L Poston

Publications and source records attributed to L Poston.

At least 91 records · Page 5Linked to original sources
PubMed1996

Isolated mesenteric arteries from pregnant rats show enhanced flow-mediated relaxation but normal myogenic tone.

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.

Airway Resistance↗
PubMed1996

Mechanism of lactate-induced relaxation of isolated rat mesenteric resistance arteries.

1. The effects of the sodium salt of the weak acid lactate on tension and intracellular pH (pH1) were studied in rat mesenteric small arteries mounted on a wire myograph. Sodium lactate was substituted iso-osmotically for sodium chloride. 2. At a concentration of 50 mM, both L- and D-stereoisomers of lactate markedly relaxed arteries preconstricted with noradrenaline (NA) within 10 min. The concentration-response relationship for L-lactate showed that the NA contracture was relaxed by 50% at approximately 26 mM. L-Lactate did not, however, relax arteries preconstricted with high-K+(45 mM) solution. 3. L-Lactate did not alter extracellular pH (pHo) but caused a small but significant decrease in pH1, measured using the pH-sensitive fluorochrome, 2',7'-bis(carboxyethyl)-5-(6)-carboxyfluorescein (BCECF). Relaxation to L-lactate was unaffected when this change in pHi was offset by the simultaneous addition of NH4Cl to the solution. 4. Sodium pyruvate (50 mM) caused a significant intracellular acidosis but did not relax arteries preconstricted with NA. 5. L-Lactate-induced relaxations were unaffected by removal of the endothelium or when the synthesis of nitric oxide (NO) was inhibited by 10(-4) M N omega-nitro-L-arginine methyl ester (L-NAME). 6. The potassium channel blockers glibenclamide (10 microM), 4-aminopyridine (3 mM) and tetraethylammonium chloride (10 mM) did not affect L-lactate-induced relaxation in arteries preconstricted with NA. Inhibition of guanylate cyclase with Methylene Blue, or cyclooxgenase with indomethacin, also did not affect relaxation to L-lactate. 7. The Rp stereoisomer of adenosine-3',5'-cyclic monophosphothioate (Rp-cAMPS), an analogue of cAMP which inhibits competitively stimulation of protein kinase A, reduced significantly L-lactate-induced relaxation at a concentration of 25 microM. Rp-cAMPS also significantly reduced forskolin-induced relaxation of the NA contracture. 8. It is concluded that L-lactate-induced relaxation in this vascular bed is pHi-1 endothelium-, and nitric oxide-independent. It is not mediated by inhibition of voltage-gated Ca2+ channels, opening of K+ channels, prostacylin or cyclic GMP. cAMP may however play a role in L-lactate-induced relaxation.

Animals↗
PubMed1996

Bradykinin-mediated relaxation of isolated maternal resistance arteries in normal pregnancy and preeclampsia.

OBJECTIVE: The aim of the study was to investigate bradykinin-mediated vasodilator function in small arteries from normotensive pregnant and nonpregnant women and from women with preeclampsia. STUDY DESIGN: Small subcutaneous arteries (approximately 250 microns luminal diameter) were dissected from biopsy specimens obtained at cesarean section from 24 normotensive pregnant women and 6 women with preeclampsia and during abdominal surgery in 15 nonpregnant women. Vascular function was assessed after arteries were mounted on a small vessel myograph. RESULTS: Preconstricted arteries from normotensive pregnant women demonstrated enhanced relaxation to bradykinin compared with those from nonpregnant women (p < 0.05), whereas arteries from women with preeclampsia showed blunted responses compared with those from normotensive pregnant women (P < 0.01). Relaxation in all groups was attenuated in the presence of the nitric oxide synthase inhibitor N omega-nitro-L-arginine so that it became similar in the three groups. Indomethacin had a small but significant inhibitory effect on bradykinin-induced relaxation, but this component of relaxation was no different among groups. Sensitivity of arteries to norepinephrine and sodium nitroprusside showed no significant differences in the three groups of women. CONCLUSION: This study provides evidence for an increase in bradykinin-mediated nitric oxide synthesis from the vascular endothelium of small arteries from the peripheral circulation of normotensive pregnant women and a relative reduction in women with preeclampsia. In turn, these changes may contribute to vasodilation in normal pregnancy and elevation of the blood pressure in preeclampsia.

Adult↗
PubMed1996

Nitric oxide is involved in flow-induced dilation of isolated human small fetoplacental arteries.

OBJECTIVES: The aim of this study was to determine the dilation that occurs in response to increments of intraluminal flow in isolated human small fetoplacental arteries and to investigate the role played by nitric oxide. STUDY DESIGN: Small fetoplacental arteries (mean luminal diameter 482 +/- 31 micrometers, n = 17, at zero flow and pressure) were dissected from samples of placental tissue obtained from normal term vaginal deliveries and elective term cesarean sections for breech presentation. The arteries were mounted on a pressure myograph, and the response to increasing intraluminal flow was investigated in the presence and absence of a nitric oxide synthase inhibitor (N-omega-nitro-L-arginine methyl ester, 10(-4) mol/L). Basal tone was assessed in a separate group of arteries (n=7) by the removal of extracellular calcium. RESULTS: The presence of significant basal tone was demonstrated in these arteries. The arteries dilated in response to increasing luminal flow, and the dilation was significantly reduced by inhibition of nitric oxide synthase (control, 5.5% +/- 1.0% increase in artery diameter, n=10, vs 0.95 +/- 0.94, n=10, in the presence of N-omega-nitro-L-arginine methyl ester, 10(-4) mol/L, p<0.01). CONCLUSIONS: The data substantiate previous indirect studies suggesting that nitric oxide plays a role in the fetoplacental circulation. Flow-induced nitric oxide release in the stem villous arteries may make an important contribution to maintenance of this low-resistance circulation.

Arginine↗
PubMed1996

Myogenic and flow-mediated responses in isolated mesenteric small arteries from pregnant and nonpregnant rats.

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.

Acetylcholine↗
PubMed1996

Mechanism of butyrate-induced vasorelaxation of rat mesenteric resistance artery.

1. The vasorelaxant effect of the sodium salt of the short chain fatty acid, butyrate, on preconstricted rat small mesenteric arteries (mean inner diameter approximately 300 microns) was characterized. Isometric force development was measured with a myograph, and intracellular pH (pHi) was simultaneously monitored, in arteries loaded with the fluorescent dye BCECF in its acetomethoxy form. Sodium butyrate (substituted isosmotically for NaCl) was applied to arteries after noradrenaline (NA) or high K+ contractures were established. 2. Arteries preconstricted with a concentration of NA inducing an approximately half maximal contraction were relaxed by 91.5 +/- 6.3% by 50 mmol l-1 butyrate. This concentration of butyrate did not, however, cause a significant relaxation of contractures to a maximal (5 mumol l-1) NA concentration, and also failed to relax significantly contractures stimulated by high (45 and 90 mmol l-1) K+ solutions. Contractures elicited with a combination of NA (at a submaximal concentration) and 45 mmol l-1 K+ were, however, markedly relaxed by butyrate. 3. Investigation of the concentration-dependency of the butyrate-induced relaxation of the half maximal NA response revealed an EC50 for butyrate of approximately 22 mmol l-1. 4. Sodium butyrate (50 mmol l-1) caused pHi to decrease from 7.25 +/- 0.02 to 6.89 +/- 0.08 (n = 4, P < 0.001). However, the vasorelaxant effect of butyrate on the submaximal NA contracture was not significantly modified when this fall in intracellular pH was prevented by the simultaneous application of NH4Cl. 5. Butyrate-induced relaxation was also unaffected by endothelial denudation and inhibition of NO synthase with N omega-nitro-L-arginine methyl ester (100 mumol l-1). 6. The relaxation of the NA contracture by 50 mmol l-1 sodium butyrate was abolished in arteries pretreated with the cyclic AMP antagonist Rp-cAMPS (25 mumol l-1). 7. We conclude that the butyrate-induced relaxation of the NA contracture is independent of intracellular acidification. The ability of Rp-cAMPS to abolish the butyrate relaxation indicates that stimulation of the cyclic AMP second messenger system may play an important role in mediating this effect.

Ammonium Chloride↗
PubMed1996

Oxidative stress and lipids in diabetes: a role in endothelium vasodilator dysfunction?

Endothelial dysfunction is a key feature of diabetes mellitus and is thought to be the major cause of vascular complications associated with the disease. The vascular endothelium demonstrates impaired synthesis of vasodilators and increased release of procoagulants and vasoconstrictors, defects which theoretically could explain the increased incidence of atherosclerosis and hypertension found within this patient group. The pathways mediating endothelial cell layer dysfunction are unknown, although many candidates have been proposed. This review concentrates on the hypothesis that increased oxidative stress combined with abnormal plasma lipid composition leads to reduced synthesis of endothelial vasodilators and hence endothelial dysfunction. Free radical generation is undoubtedly raised in diabetes but the evidence for decreased antioxidant status is debatable. The role of antioxidant and lipid-lowering therapy is considered, but few studies have directly investigated the effect of treatment on vascular function. Concern arises from individual studies of vitamin E in diabetic animals which have proved deleterious. Current literature implies that a combination therapy of vitamin E and vitamin C may be beneficial, but this needs to be investigated further in both animal and human diabetes.

Animals↗
PubMed1995

Control of vascular resistance in the maternal and feto-placental arterial beds.

This review aims to provide a comprehensive summary of the mechanisms involved in the physiological adaptation of the vasculature to pregnancy. Profound changes occur both systemically and in discrete circulations in the mother, but it is debatable which factors are responsible. Similarly, whilst the feto-placental circulation must be substantially controlled by humoral mechanisms, the exact role of each potential contributor is not known. In view of the hitherto unappreciated and very important role of the endothelium-derived vasodilator, nitric oxide, in the control of peripheral vascular resistance, considerable emphasis will be placed on the many recent investigations in this area.

Animals↗
PubMed1995

Selective impairment of acetylcholine-mediated endothelium-dependent relaxation in isolated resistance arteries of the streptozotocin-induced diabetic rat.

1. There is growing evidence that an impairment in the function of nitric oxide synthase may play a role in the vascular complications of diabetes mellitus. The relaxation of resistance arteries from the mesenteric and hindlimb circulations of streptozotocin-induced diabetic rats and age-matched controls were investigated using two endothelium-dependent vasodilators, bradykinin and acetylcholine, and the endothelium-independent vasodilator sodium nitroprusside. The contractile responses to the alpha 1-adrenergic agonist phenylephrine were also studied. 2. Endothelium-dependent relaxation to acetylcholine was impaired in the diabetic rats in arteries from both mesenteric and hindlimb circulations (hindlimb pEC50, 7.93 +/- 0.08 in the control compared with 7.38 +/- 0.10 in the diabetic rat; mesenteric pEC50, 7.47 +/- 0.04 in the control compared with 6.65 +/- 0.06 in the diabetic rat; unpaired t-test P < 0.0001). Bradykinin elicited relaxation in only the mesenteric arteries, and this was not attenuated in the diabetic rats compared with controls. 3. Endothelium-independent relaxation to sodium nitroprusside was similar in the two circulations and was not abnormal in the diabetic rats. There was no significant difference in constrictor responses to phenylephrine between diabetic rats and controls in either the hindlimb or mesenteric arteries, in contrast to an earlier study in which we showed increased sensitivity to noradrenaline. 4. The diabetic rats therefore demonstrated a specific impairment of receptor-mediated endothelium-dependent relaxation to acetylcholine. These results suggest that, in this diabetic model, the ability of the endothelium to relax arteries via nitric oxide may involve a defect of a specific signal transduction pathway, leading to reduced production of nitric oxide.

Acetylcholine↗
PubMed1995

Nitric oxide synthase activities in placental tissue from normotensive, pre-eclamptic and growth retarded pregnancies.

OBJECTIVE: To measure nitric oxide synthase activity in tissues from the placenta, placental bed and umbilical cord at delivery in normal and complicated pregnancies. DESIGN: A prospective blinded study. SETTING: The obstetric departments of three London teaching hospitals. SUBJECTS: Samples of whole placenta, dissected stem villous arteries, umbilical cord vessels and the placental bed of the uterus were collected at delivery and assayed for nitric oxide synthase activity. Samples of placenta were taken from ten normotensive, six pre-eclamptic and eight growth retarded pregnancies, and stem villous arteries from a further seven normotensive pregnancies. RESULTS: There was minimal placental bed nitric oxide synthase activity in each group. Placental villous homogenates from pregnancies complicated by pre-eclampsia and fetal growth retardation had significantly lower activities of nitric oxide synthase than those from normotensive women with appropriately grown babies. There were no significant differences in calcium dependent or calcium independent nitric oxide synthase activities in the umbilical vein and artery in the normal or in the pre-eclamptic groups. However, there was significantly more calcium dependent than calcium independent nitric oxide synthase in the umbilical veins in all groups. CONCLUSIONS: Local nitric oxide production in the placental bed of the uterus is unlikely to contribute substantially to the low resting vascular tone in the uteroplacental circulation. However, a relative deficiency of placental nitric oxide in pregnancies complicated by fetal growth retardation and pre-eclampsia may contribute to the development of the high impedance fetoplacental circulation found in these conditions.

Female↗
PubMed1995

Mechanisms of pHi control and relationships between tension and pHi in human subcutaneous small arteries.

Intracellular pH (pHi) control and relationships between pHi and tension have been investigated in human subcutaneous small arteries. Isometric tension and pHi (using 2',7'-bis(carboxyethyl)- 5(6)-carboxyfluorescein) were estimated simultaneously. pHi recovery from an acute acid load was dependent on external Na+ and partially inhibited by the absence of HCO3(-) [N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered solution] or by the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). In an HCO3(-)-buffered physiological salt solution (PSS), pHi recovery was partially blocked by hexamethylene amiloride (HMA), an inhibitor of Na+/H+ exchange, and completely blocked by DIDS and HMA together. Intracellular Cl- depletion of arteries did not affect the rate of pHi recovery in PSS from an acid load. pHi recovery from acute alkalosis was unaffected by external Na+ removal, reduced in HEPES buffer, and abolished by removal of external Cl-. These data suggest that human small arteries maintain pHi by Na+/H+ exchange and Na(+)-dependent HCO3(-) exchange in response to an acid load, and Na(+)-independent Cl-/HCO3(-) exchange to counteract intracellular alkalosis. Norepinephrine (NE)-, endothelin-1 (ET-1)-, arginine vasopressin (AVP)-, and K(+)-induced tension did not alter pHi in PSS, but there was a small fall with angiotensin II (ANG II). In HEPES, stimulation with K+, NE, ANG II, or AVP led to a fall in pHi, but this did not occur with ET-1. It is therefore unlikely in vivo that an increase in pHi in these arteries would be involved in either tension development or growth induced by these agonists.

Acetates↗
PubMed1994

Effect of flosequinan on human small subcutaneous arteries.

We have investigated the effect of the novel hypotensive agent, flosequinan, on human small artery constrictor function. Concentration-dependent tension development to both noradrenaline and K+ was reduced in the presence of flosequinan. Arteries pre-contracted with noradrenaline demonstrated a greater concentration-dependent relaxation to flosequinan than did those pre-contracted with K+. Flosequinan depressed the sensitivity to extracellular Ca2+ of arteries pre-contracted with noradrenaline, but this effect was less marked in arteries pre-contracted with K+. These data support previous studies which suggest that flosequinan may affect receptor-mediated contraction by reducing Ca2+ sensitivity.

Adult↗
PubMed1994

Endothelium-dependent relaxation of human resistance arteries in pregnancy.

OBJECTIVE: Reduced peripheral vascular resistance is an integral component of vascular adaptation in pregnancy. The precise mediators of the reduced resistance are unknown, however, and are often assessed by indirect means. In this study we investigated endothelium-dependent relaxation directly by examining acetylcholine-mediated relaxation in small arteries dissected from the subcutaneous fat layer undergoing biopsy at the time of gynecologic surgery and cesarean section. STUDY DESIGN: By means of a small vessel myograph we measured tension in resistance arteries of normal pregnant (n = 22) and nonpregnant (n = 10) women and assessed the contributions of vasodilatory prostanoids and endothelium-derived relaxing factor on endothelium-dependent relaxation, as elicited by acetylcholine (1 nmol/L to 10 mumol/L) after precontraction with 3 mumol/L norepinephrine. RESULTS: Endothelium-dependent relaxation was similar in arteries of pregnant and nonpregnant women. Sodium nitroprusside-induced relaxation was similar in arteries of pregnant and nonpregnant women. CONCLUSION: This study fails to demonstrate any increase in acetylcholine-induced endothelium-dependent relaxation in small subcutaneous arteries in pregnancy.

Acetylcholine↗
PubMed1994

Functional characteristics of small placental arteries.

OBJECTIVES: The aim of this study was to investigate characteristics of placental arteries capable of influencing vasomotor tone in the fetoplacental vascular bed. Contractile characteristics and endothelium-dependent and endothelium-independent relaxation were examined. STUDY DESIGN: By means of a small vessel myograph arteries of mean normalized internal diameter 353.22 +/- 13.14 microns were studied under isometric conditions. Contractile function was assessed with a variety of agonists, including angiotensin II, endothelin-1, the thromboxane mimetic U46619, prostaglandin E2, and prostaglandin F2 alpha. The effect of physiologic and supraphysiologic PO2 on vascular function was also examined. Relaxation was assessed in response to known endothelium-dependent vasodilators, including acetylcholine, bradykinin, histamine, and A23187 and to sodium nitroprusside (endothelium independent). The effect of indomethacin and the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester on contractile function was also evaluated. RESULTS: Sensitivity to sodium nitroprusside was reduced by a high PO2. U46619 was the most potent constrictor agonist studied. The response of precontracted arteries to known endothelium-dependent vasodilators was minimal, other than for histamine, which led to modest relaxation. The constrictor response to U46619 was increased in the presence of NG-nitro-L-arginine methyl ester. CONCLUSIONS: Oxygen tension may be an important determinant of relaxation in small placental arteries. Receptor-mediated release of endothelium-derived relaxing factor is not a major mechanism in the fetoplacental circulation.

Arteries↗