Cortisol inhibits cholinergic vasodilatation in the human forearm

Mangos, George; Walker, Brian R.; Kelly, John J.; Lawson, J A; Webb, David J.; Whitworth, Judith A.

doi:10.1016/s0895-7061(00)01201-2

Cited by 111 publications

(79 citation statements)

References 27 publications

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“…Cortisol did not affect the response to sodium nitroprusside, and although N G -monomethyl-L-arginine inhibited cholinergic vasodilation in placebo-treated subjects, it had no additional effect in the presence of cortisol. 6 Taken together, these results are consistent with a role for abnormalities of the nitric oxide system in cortisol-induced hypertension in humans.…”

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confidence: 75%

l -Arginine Transport in Humans With Cortisol-Induced Hypertension

et al. 2003

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Abstract-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 mol/L), incorporating 100 nmol/L [ 3 H]-L-arginine for a period of 5 minutes at 37°C. Forearm Key Words: cortisol Ⅲ hypertension, mineralocorticoid Ⅲ nitric oxide Ⅲ arginine Ⅲ human C ortisol, the major naturally occurring human glucocorticoid, is implicated in the pathogenesis of some forms of essential hypertension, 1 but the mechanisms by which cortisol raises blood pressure are not fully defined. Cardiac output is increased but is not essential for the increase, 2 and sympathetic activity is, if anything, decreased. 3 A role for the nitric oxide system in cortisol-induced hypertension has been implicated in animal models of cortisol-induced hypertension; L-arginine, the substrate precursor to nitric oxide, prevents and reverses the development of adrenocorticotropin-induced hypertension in rats. 4 In humans, cortisol-increases in blood pressure occur in association with reductions in plasma nitrate/nitrite concentrations, but no change in plasma arginine or symmetric or asymmetric dimethyl arginine has been observed, indicating that the reductions in nitrate could not be explained by changes in substrate availability or endogenous nitric oxide synthase inhibitors. 5 More recently, using bilateral forearm plethysmography, we have found impaired cholinergic vasodilatation after cortisol administration. Cortisol did not affect the response to sodium nitroprusside, and although N G -monomethyl-L-arginine inhibited cholinergic vasodilation in placebo-treated subjects, it had no additional effect in the presence of cortisol. 6 Taken together, these results are consistent with a role for abnormalities of the nitric oxide system in cortisol-induced hypertension in humans.In the current study, we explored whether cortisol reduces the cellular uptake of L-arginine and whether this mechanism might provide an explanation for the decreased synthesis or secretion of nitric oxide. The study was performed in healthy adult men against a background of a restricted-nitrate diet. L-Arginine transport was assessed in peripheral blood mononuclear cells isolated from these subjects as well as in vivo in the forearm vascular bed. Methods SubjectsHealthy (or disease-free) men were recruited by advertisement. All underwent a physical medical examination and had their medical history recorded. Persons with a history of major illness, including diabetes, cardiovascular disease, respiratory illness, and any contraindication to corticosteroid therapy...

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confidence: 75%

l -Arginine Transport in Humans With Cortisol-Induced Hypertension

et al. 2003

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“…The results of our correlation analysis are in accordance with findings of Akaza et al [15] who showed a significant negative correlation between percentage changes in brachial artery diameter during flow mediated dilatation and morning cortisol levels in patients of CS. Although morning serum cortisol level is not considered to be a disease marker in CS due to its inherent inter-individual variations independent of the disease status, our findings indicate the probable pathophysiologic role excess cortisol levels can play in the causation of vascular endothelial dysfunction as already been shown by previous studies [9][10][11].…”

Section: Discussionsupporting

confidence: 55%

“…MP150 (BIOPAC Systems Inc., CA, USA), a computer based digital data acquisition system with Ethernet interfacing and software Acqknowledge® 3.8.2 was employed to record ECG and PPG signals at a sampling rate of 1kHz. PPG acquisition unit essentially comprised of an infrared (860±6 nm), reflection type photoelectric transducer (TSD200) and a biopotential amplifier (PPG100C) with a preset of gain and acetate [11], based on forearm blood flow responses to reactive hyperemia and intra-arterially infused acetylcholine respectively. In both these studies patients and subjects were shown to be free of any of the clinical or biochemical features of glucocorticoid induced metabolic syndrome suggesting that excess glucocorticoid levels can per se affect vascular endothelial function.…”

Section: Assessment Of Vascular Functionmentioning

confidence: 99%

Impaired endothelium mediated vascular reactivity in endogenous Cushing's syndrome

et al. 2011

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“…Furthermore, it has been shown that glucocorticoids, more particularly cortisol, induce a downregulation of eNOS in endothelial cells as well as a decrease in plasma NOx levels (Wallerath et al, 1999;Rogers et al, 2002). Chronic cortisol administration to healthy human controls is also associated with decreased endothelium-dependent flow-mediated dilatation, which reflects endothelial NO production (Mangos et al, 2000). The HPA axis hyperactivity found in MD could therefore be responsible, at least partially, for the endothelial and platelet NO dysregulations observed in MD patients, which in turn could mediate some of the deleterious CV effects of HPA hyperactivity in MD patients.…”

Section: Discussionmentioning

confidence: 99%

Alteration of Decreased Plasma NO Metabolites and Platelet NO Synthase Activity by Paroxetine in Depressed Patients

Chrapko

Jurasz

Radomski

et al. 2005

Neuropsychopharmacol

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Although major depression (MD) and cardiovascular disease (CVD) have been conclusively linked in the literature, the mechanism associating MD and CVD is yet undetermined. The purpose of this paper is to further investigate a potential mechanism involving nitric oxide (NO) and to examine the effect of the selective serotonin reuptake inhibitor paroxetine on NO production by both platelets and the endothelium. In total, 17 subjects with MD and 12 healthy controls (HCs) with no known history of cardiovascular illness completed the study. Paroxetine was administered to both the MD patients and HCs over an 8-week period, and then medication was discontinued. Blood samples were taken at various times throughout paroxetine treatment and after discontinuation. Plasma NO metabolite (NOx) levels were measured by a chemiluminescence method. Platelet endothelial NO synthase (eNOS) activity was examined through the conversion of L-[14 C]arginine to L-[ 14 C]citrulline. Data were analyzed using t-tests and a linear mixed effects model. Baseline levels of both plasma NOx and platelet NOS activity were significantly lower in subjects with MD compared to HCs. Throughout paroxetine treatment, plasma NOx levels increased in both HCs and MD patients. However, platelet eNOS activity decreased in HCs, while no statistically significant change was evidenced in MD patients. These data suggest that, in MD patients, decreased peripheral production of NO, a potential contributor to increased cardiovascular risk, is modified by administration of the antidepressant paroxetine.

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Cortisol inhibits cholinergic vasodilatation in the human forearm

Cited by 111 publications

References 27 publications

l -Arginine Transport in Humans With Cortisol-Induced Hypertension

l -Arginine Transport in Humans With Cortisol-Induced Hypertension

Impaired endothelium mediated vascular reactivity in endogenous Cushing's syndrome

Alteration of Decreased Plasma NO Metabolites and Platelet NO Synthase Activity by Paroxetine in Depressed Patients

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