The nitric oxide system in glucocorticoid-induced hypertension

Abstract

The blood pressure-raising effects of adrenocortical steroids with predominantly glucocorticoid activity, both naturally occurring and synthetic, are well known. Recent evidence suggests that the nitric oxide system plays a key role in the hypertension produced by glucocorticoids. Glucocorticoid actions at various sites in the nitric oxide synthase (NOS) pathway may result in elevated blood pressure. These include: alterations in l-arginine availability or transport; NOS2 and NOS3 downregulation; reduced cofactor bioavailability; NOS uncoupling; a concomitant elevation in reactive oxygen species and removal of nitric oxide (NO) from the vascular environment; alterations in whole body antioxidant status; and erythropoietin induced resistance to NO.

GTP Cyclohydrolase 1 Downregulation Contributes to Glucocorticoid Hypertension in Rats

“…6 To examine the genomic effect of glucocorticoids on GTPCH1 and eNOS, we performed mRNA expression studies. We have previously shown that GTPCH1 mRNA levels were significantly decreased (50% of controls) in aortic segments incubated with dexamethasone (1.3ϫ10 Ϫ6 mol/L) after 6 hours.…”

“…1,4,5 A reduction in the bioavailability of NO, a potent vasodilator, has been implicated in glucocorticoid-induced hypertension, and glucocorticoids affect many proteins involved in NOmediated vasodilation. 6 NO plays a key role in vascular tone, and decreases in NO production and bioavailability have been shown to reduce endothelium-dependent dilation and increase blood pressure. NO can be produced by the conversion of arginine and oxygen to citrulline via 3 isoforms of NO synthase (NOS).…”

Corticosteroid receptors, macrophages and cardiovascular disease

“…Oxidative stress and nitric oxide deficiency are emerging as key components in the pathogenesis of glucocorticoid-induced hypertension (Ong et al 2008). Nitric oxide deficiency in models of glucocorticoidinduced hypertension is thought to be due to decreased L-arginine availability and reduced endothelial nitric oxide synthase and inducible nitric oxide synthase gene expression (Whitworth et al 2002). Together, these findings highlight the role of inflammation and oxidative stress in the pathogenesis of glucocorticoidinduced hypertension.…”

Glucocorticoid-Mediated Hypertension

“…1,7 Administration of glucocorticoids to mice resulted in a decrease in the serum NO metabolites NO 2 Ϫ and NO 3 Ϫ , an indirect indicator of serum NO levels, and a reduction in endothelial NO synthase III mRNA abundance in aorta, liver, and kidney as a result of decreased transcription and increased degradation. 1,7 Glucocorticoid-and ACTH-mediated hypertension in rats can be mitigated by L-arginine, the precursor to NO, and the L-arginine effect can be blocked by NO synthetase inhibition. 7,8 Finally, endothelial NO null mice do not develop hypertension when given dexamethasone.…”

“…1,7 Glucocorticoid-and ACTH-mediated hypertension in rats can be mitigated by L-arginine, the precursor to NO, and the L-arginine effect can be blocked by NO synthetase inhibition. 7,8 Finally, endothelial NO null mice do not develop hypertension when given dexamethasone. 9 These findings are consistent with a role for NO in mediating the hypertension by glucocorticoids.…”