Glucocorticoid-induced hypertension and the nitric oxide system

Abstract

Glucocorticoid hormones, both naturally occurring and synthetic, have long been recognized as a major cause of hypertension. There are well-described experimental models of glucocorticoid-induced hypertension, such as adrenocorticotropic hormone- and dexamethasone-induced hypertension in rats, although the exact mechanism of glucocorticoid-induced hypertension remains unclear. It was initially considered to be due to mineralocorticoid receptor activation but more recent studies have not supported this notion. Current evidence demonstrates the importance of the nitric oxide (NO) system and interactions between NO and reactive oxygen species in the development of glucocorticoid-induced hypertension. This review highlights the pathways contributing to NO deficiency, which encompass the availability of l-arginine, endothelial NO synthase function and the extent of NO inactivation during oxidative stress.

Keywords::

• adrenocorticotropic hormone
• corticosterone
• cortisol
• dexamethasone
• hypertension
• l-arginine
• nitric oxide
• nitric oxide synthase
• oxidative stress
• superoxide

Financial & competing interests disclosure

The work of the authors was supported by the National Health and Medical Research Council of Australia Project Grant (418026) and the Clive & Vera Ramaciotti Foundations Establishment Grant, research scholarships from the Heart Foundation of Australia (PB07C3427) and the Royal Australasian College of Physicians Research and Education Foundation (Jacquot Research Entry Scholarship). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.