l -Arginine Transport in Humans With Cortisol-Induced Hypertension

Abstract

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...

Reactive Oxygen Species and Glucocorticoid‐induced Hypertension

“…Despite these findings, evidence for these processes in cortisol‐induced hypertension in human is lacking. l ‐Arginine transport was intact and l ‐arginine supplementation did not lower cortisol‐induced elevation in BP 33 …”

Arginase II inhibition prevents nitrate tolerance

“…Cellular 3 H‐L‐arginine uptake was measured as previously described (Chin‐Dusting et al ., 2003; Parnell et al ., 2004; Zhang et al ., 2006). Briefly, EA.hy926 cells were plated in 24‐well, flat bottom, tissue culture plates and grown to ≈ 90% confluence at 37 °C in 5% CO 2 .…”

The Role of Amino Acids in the Modulation of Cardiac Metabolism During Ischemia and Heart Failure

“…Several studies have previously examined the role of arginine supplementation on endothelial function in HF [127,128]. These results have demonstrated varying positive effects on endothelial function, probably due to substantial variations in the timing and dose of arginine [128].…”

“…These results have demonstrated varying positive effects on endothelial function, probably due to substantial variations in the timing and dose of arginine [128]. It has been hypothesized that the limitation of arginine availability for NO biosynthesis, plays a pivotal role in the development of endothelial dysfunction in HF subjects.…”