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Jaye P F Chin-Dusting

Publications and source records attributed to Jaye P F Chin-Dusting.

10 recordsLinked to original sources
PubMed2006

Role of the endothelium on vasoactive agents in patients with liver cirrhosis.

BACKGROUND AND AIM: Patients with liver cirrhosis exhibit peripheral vasodilatation and decreased vasoconstrictor responsiveness. We investigated the role of the endothelium in these patients. METHODS: Nine patients with cirrhosis and seven controls were recruited. Responses to acetylcholine, bradykinin and sodium nitroprusside were obtained using forearm plethysmography. Responses to norepinephrine (100 ng/min) were obtained in the absence and combined presence of the cyclo-oxygenase inhibitor, indomethacin, and the nitric oxide (NO) synthase inhibitor, N(G)-monomethyl-L-arginine. RESULTS: Responses to acetylcholine (area under curve: controls vs cirrhotic, 10326 +/- 1400 vs 18490 +/- 2787 units; P = 0.036), but not to bradykinin (15619 +/- 3557 vs 12415 +/- 3823 units) or sodium nitroprusside, were significantly higher in patients with cirrhosis. Responses to norepinephrine were significantly dampened in cirrhotics (percentage increase in forearm blood flow; controls vs cirrhotics, -50.50 +/- 2.69 vs-26.39 +/- 5.44; P = 0.036) but this blunted response was no longer apparent following the administration of both blockers. CONCLUSIONS: We conclude that: (i) there is an increased response to acetylcholine but not to bradykinin; and (ii) that an enhanced production of prostacyclin and/or NO is responsible for the dampened response to norepinephrine.

Acetylcholine↗
PubMed2005

Responses to neither exogenous nor endogenous endothelin-1 are altered in patients with hypercholesterolemia.

There is some controversy regarding whether vascular responses to endothelin are altered in hypercholesterolemia. Studies performed to date have been compromised by the use of endothelin antagonists at inappropriate concentrations. In the current study, we examine the role of endothelin-1 in hypercholesterolemic patients using lower, more selective doses of specific endothelin antagonists. Twenty-two patients with hypercholesterolemia (total plasma cholesterol > 6.0 mmol/l) and 17 healthy controls were recruited. Forearm vascular responses to endothelin-1 (5 pmol/min), the endothelin A antagonist BQ-123 (10 nmol/min), and the endothelin B antagonist BQ-788 (1 nmol/min) were obtained. Endothelin-1 caused a significant vasoconstriction in both hypercholesterolemic and control subjects, an effect that was not significantly different between the two groups (P = 0.784). BQ-123 caused a significant vasodilatation that was not significantly different between the two groups (P = 0.899). Similarly, responses to BQ-788 (P = 0.774) and mean plasma endothelin-1 levels were not different (control vs. hypercholesterolemia, 1.16 +/- 0.18 vs. 1.06 +/- 0.15 fmol/ml; P = 0.64). Responses to neither exogenous nor endogenous endothelin are influenced by plasma cholesterol levels in humans. It is thus unlikely that the endothelin system contributes to early vascular disease pathology in patients with hypercholesterolemia.

Blood Pressure↗
PubMed2004

In vivo and in vitro evidence for ACh-stimulated L-arginine uptake.

Whereas L-arginine is clearly recognized as the precursor for nitric oxide synthesis, and its entry into endothelial cells via system y(+) transport is established, few data exist regarding the acute regulation of this transport process. We specifically investigated the effect of ACh and isoprenaline (Iso) on L-arginine uptake in the human forearm and in cultured bovine aortic endothelial cells (BAEC). Sixteen healthy males were studied. During a steady-state intra-arterial infusion of [(3)H]L-arginine (100 nCi/min), the effects of ACh (9.25 and 37 microg/min), Iso (25-50 and 200 microg/min), and sodium nitroprusside (SNP) (1-2 and 8 microg/min) on forearm plasma flow (FPF), L-[(3)H]arginine uptake, and L-[(3)H]citrulline release were determined. In parallel experiments, the effects of ACh, Iso, and SNP on L-[(3)H]arginine uptake were studied in BAEC. L-Arginine uptake was inversely related to FPF (r = -0.50; P < 0.005). At a similar FPF (ACh 56.82 +/- 9.25, Iso 58.49 +/- 5.56, SNP 57.92 +/- 4.96 ml/min; P = ns), intra-arterial ACh significantly increased forearm uptake of L-[(3)H]arginine (54,655 +/- 8,018 dpm/min), compared with that observed with either Iso (40,517.23 +/- 6,841 dpm/min; P = 0.01) or SNP (36,816 +/- 4,650 dpm/min; P = 0.011). This was associated with increased ACh-induced L-[(3)H]citrulline release compared with Iso and SNP (P = 0.046). Similarly, in BAEC, ACh significantly increased L-[(3)H]arginine uptake compared with control, Iso, or SNP (ACh 12.0 x 10(7) +/- 1.83 x 10(7) vs. control 6.67 x 10(7) +/- 1.16 x 10(7) vs. Iso 7.35 x 10(7) +/- 1.63 x 10(7) vs. SNP 6.01 x 10(7) +/- 1.11 x 10(7) fmol.min(-1).mg(-1) at 300 micromol/l L-arginine; P = 0.043). Taken together, these data indicate that ACh stimulates L-arginine uptake in cultured endothelial cells and in human forearm circulation, indicating the potential for acute modulation of endothelial L-arginine uptake.

Acetylcholine↗
PubMed2004

Plasma C-reactive protein, but not protein S, VCAM-1, von Willebrand factor or P-selectin, is associated with endothelium dysfunction in coronary artery disease.

Abnormal endothelium-dependent vasodilatation is well documented in coronary artery disease (CAD), as are significant increases of acute phase inflammatory proteins and other soluble hepatic and endothelium derived proteins. In the current study we investigated whether there is a relationship between endothelium-dependent vasodilatation and the plasma levels of such proteins. Further we examined the association between these proteins, together with age, cholesterol and endothelium function, and participant status (i.e. healthy, smoker, coronary artery disease). Three groups of participants were recruited: healthy controls (n = 20), cigarette smokers (n = 20) and patients with coronary artery disease (n = 20). Forearm vascular dilatation responses to the endothelium-dependent agonist acetylcholine were obtained using venous occlusion plethysmography. Blood was sampled at the time of study for the measurement of the serological proteins described above. Responses to acetylcholine were significantly dampened in patients with CAD when compared with control and smoker groups (forearm blood flow at acetylcholine 37 microg/min): control, smokers, CAD, 12.14 +/- 2.14, 12.35 +/- 09.4, 5.12 +/- 0.81, ANOVA, P < 0.05). Responses to acetylcholine were not different between controls and smokers. C-reactive protein (C-RP) levels (controls, smokers, CAD, 1.40 +/- 0.19, 2.27 +/- 0.71, 4.73 +/- 1.09, P < 0.05) and protein S levels were significantly higher in the CAD group compared with the other two groups. There was a significant inverse correlation between forearm blood flow responses to acetylcholine and C-reactive proteins. Both responses to acetylcholine and C-RP levels demonstrated a significant association with participant status with the r value increasing from 0.405 for responses to acetylcholine to 0.491 for the combination of responses to acetylcholine and C-RP. We conclude that there is an inverse correlation between C-reactive protein, but not protein S, VCAM-1, P-selectin nor von Willebrand factor, levels and abnormal endothelium-dependent vasodilation and further that responses to acetylcholine together with C-RP protein have a strong association with cardiovascular risk and disease.

Acetylcholine↗
PubMed2004

An age-related decline in endothelial function is not associated with alterations in L-arginine transport in humans.

OBJECTIVES: Endothelial dysfunction is established in aged individuals; however, the mechanism(s) are not fully elucidated. We have previously identified l-arginine transport as a potential rate-limiting factor in nitric oxide (NO) production in heart-failure patients, characterized with endothelial dysfunction. We therefore aimed to investigate whether the age-related decline in endothelial function is due to reduced transport of the NO precursor, L-arginine. METHODS: Thirty-seven healthy males aged between 19 and 69 were recruited. Throughout 40 min of intra-arterial (i.a.) infusion of [3H]L-arginine (100 nCi/min), venous blood samples were withdrawn for the determination of L-arginine clearance. Venous occlusion plethysmography was then used to record the forearm blood flow responses to i.a. infusions of acetylcholine (ACh; 9.25 and 37 microg/min) and sodium nitroprusside (SNP; 2 and 8 microg/min). RESULTS: While ACh-induced vasodilation decreased with age (37 microg/min; young 15.87 +/- 1.30, middle-aged 9.59 +/- 1.33, older 10.42 +/- 1.12 ml/min per 100 ml tissue; P = 0.001), there was no change in forearm [3H]L-arginine clearance (young 126.08 +/- 19.05, middle-aged 122.47 +/- 20.96, older 126.56 +/- 19.56 ml/min; NS). Further [3H]L-arginine uptake studies in isolated peripheral blood mononuclear cells supported our in vivo findings, demonstrating no difference in [3H]L-arginine transport across the age spectrum. CONCLUSIONS: The present study excludes the hypothesis of impaired L-arginine transport as a potential mechanism for the age-related decline in endothelial function.

Acetylcholine↗
PubMed2003

Impaired acetylcholine-induced release of nitric oxide in the aorta of male aromatase-knockout mice: regulation of nitric oxide production by endogenous sex hormones in males.

The consequences of estrogen deficiency on the cardiovascular system have been widely examined in females. The effects of endogenous estrogen deficiency in males are less clear. The aromatase-knockout (ArKO) mouse lacks a functional Cyp19 gene, which encodes aromatase, and is thus incapable of synthesizing endogenous estrogen. In the present study, we examined the effect of lack of endogenous estrogens on vascular function in aortic rings isolated from male ArKO mice and compared these effects to rings from wild-type (WT) littermates. Full concentration-response curves to norepinephrine, acetylcholine, isoprenaline, and sodium nitroprusside were obtained in the absence and presence of the nitric oxide synthase inhibitor Nomega-nitro-L-arginine in aortic segments set up in isometric myographs. Responses to noradrenaline were not different in aorta from ArKO compared with WT mice. Both Nomega-nitro-L-arginine and endothelium denudation significantly shifted the noradrenaline concentration-response curve to the left; however, this shift was not different in ArKO compared with WT. Responses to the endothelium-dependent vasodilator acetylcholine were significantly blunted in aortic rings from ArKO mice (Emax, 58.2+/-0.9% and 34.0+/-0.5% in wild-type and ArKO, respectively; P<0.05), whereas responses to the endothelium-independent agonist sodium nitroprusside and to the partial endothelium-dependent agonist isoprenaline were not affected. These findings suggest that endogenous estrogen facilitate vasorelaxation in males. This may be via modulating endothelial function rather than vascular smooth muscle cell responsiveness.

Acetylcholine↗
PubMed2003

L-arginine transport in humans with cortisol-induced hypertension.

A deficient L-arginine-nitric oxide system is implicated in cortisol-induced hypertension. We investigate whether abnormalities in L-arginine uptake contribute to this deficiency. Eight healthy men were recruited. Hydrocortisone acetate (50 mg) was given orally every 6 hours for 24 hours after a 5-day fixed-salt diet (150 mmol/d). Crossover studies were performed 2 weeks apart. Thirty milliliters of blood was obtained for isolation of peripheral blood mononuclear cells after each treatment period. L-arginine uptake was assessed in mononuclear cells incubated with L-arginine (1 to 300 micromol/L), incorporating 100 nmol/L [3H]-l-arginine for a period of 5 minutes at 37 degrees C. Forearm [3H]-L-arginine extraction was calculated after infusion of [3H]-L-arginine into the brachial artery at a rate of 100 nCi/min for 80 minutes. Deep forearm venous samples were collected for determination of L-arginine extraction. Plasma cortisol concentrations were significantly raised during the active phase (323+/-43 to 1082+/-245 mmol/L, P<0.05). Systolic blood pressure was elevated by an average of 7 mm Hg. Neither L-arginine transport into mononuclear cells (placebo vs active, 26.3+/-3.6 vs 29.0+/-2.1 pmol/10 000 cells per 5 minutes, respectively, at an l-arginine concentration of 300 micromol/L) nor L-arginine extraction in the forearm (at 80 minutes, placebo vs active, 1 868 904+/-434 962 vs 2 013 910+/-770 619 disintegrations per minute) was affected by cortisol treatment; ie, that L-arginine uptake is not affected by short-term cortisol treatment. We conclude that cortisol-induced increases in blood pressure are not associated with abnormalities in the l-arginine transport system.

Adult↗
PubMed2003

Low-dose atorvastatin therapy does not augment endothelial function in active hypercholesterolaemic males.

AIMS: As statin therapy has been demonstrated to augment endothelial function in sedentary hypercholesterolaemia (HC), we aimed to investigate the effects of atorvastatin therapy on endothelial function in physically active, HC men. METHOD AND RESULTS: Eleven physically active, HC males were recruited. Endothelial function [forearm blood flow response to brachial artery infusion of acetylcholine (Ach)] was assessed twice in each subject following atorvastatin or no therapy in a randomized crossover design. In addition, endothelial function was compared with an active, normolipidaemic control group (C). Atorvastatin therapy reduced total and LDL cholesterol, but had no effect on basal blood flow or endothelial function (peak ACh mean difference +/- standard error 0.75 +/- 1.75 ml min(-1) per 100 ml tissue) [95% confidence interval (CI) -3.1, 4.6]. In addition, there was no difference in endothelial function between the HC and C groups (-1.14 +/- 2.60 ml min(-1) per 100 ml tissue; CI -6.53, 4.25). CONCLUSION: Statin therapy in HC patients with normal endothelial function does not augment endothelial function.

Anticholesteremic Agents↗
PubMed2003

Current pharmacotherapy in the management of cirrhosis: focus on the hyperdynamic circulation.

Many major complications of hepatic cirrhosis relate to the development of a characteristic hyperdynamic circulatory state in these patients, irrespective of the underlying disease aetiology. Vasodilatation of the systemic and splanchnic circulations leads to a reduced total systemic vascular resistance, increased cardiac output and intense activation of neurohumoral vasoconstrictor systems including the sympathetic nervous system, renin-angiotensin system and vasopressin. Vasoconstriction of the renal and hepatic circulations contributes to the development of renal failure and portal hypertension, respectively. Current treatments that focus on amelioration of these circulatory derangements offer much promise, however, they are often limited by side effects in these patients.

Adrenergic beta-Antagonists↗