Glucocorticoids and Cardiovascular Disease

Abstract

Chronic excessive activation of glucocorticoid receptors induces obesity, insulin resistance, glucose intolerance, dyslipidaemia and hypertension. Subtle abnormalities of the hypothalamic-pituitaryadrenal axis and/or of tissue sensitivity to glucocorticoids are also associated with these cardiovascular risk factors in patients with the metabolic syndrome. Furthermore, glucocorticoids have direct effects on the heart and blood vessels, mediated by both glucocorticoid and mineralocorticoid receptors and modified by local metabolism of glucocorticoids by the 11b-hydroxysteroid dehydrogenase enzymes. These effects influence vascular function, atherogenesis and vascular remodelling following intravascular injury or ischaemia. This article reviews the systemic and cardiovascular effects of glucocorticoids, and the evidence that glucocorticoids not only promote the incidence and progression of atherogenesis but also modify the recovery from occlusive vascular events and intravascular injury. The conclusion is that manipulation of glucocorticoid action within metabolic and cardiovascular tissues may provide novel therapeutic avenues to combat cardiovascular disease.European Journal of Endocrinology 157 545-559

Chronic blockade of hindbrain glucocorticoid receptors reduces blood pressure responses to novel stress and attenuates adaptation to repeated stress

“…There is growing evidence that both stress and glucocorticoids contribute to the etiology of cardiovascular disease; however, the role of glucocorticoids in the stress response has long been a matter of debate (1,3,5,13,15,28,30,31,35,36,38,39,42,48,49,52,58,61,65,67,68,70,71). Recent research has led to the general hypothesis that stress-induced increases in glucocorticoids act in the brain to prepare the organism for future events (12,52).…”

“…Acute stress rapidly increases blood pressure, heart rate, plasma glucocorticoid concentration, and blood glucose levels (8), while chronic or repeated stress is associated with increases in baseline blood pressure and glucocorticoids (17). Chronically elevated glucocorticoids increase morbidity and mortality from cardiovascular disease and alterations in the glucocorticoid receptor (GR), and in glucocorticoid metabolizing enzymes are associated with hypertension and cardiovascular disease in humans (28,30,35,36,39,48,49,61,65,67,70,71). Thus, chronic stress-induced elevations in glucocorticoids likely contribute to the adverse effects of stress on cardiovascular health.…”

Coronary Artery Spasm, Hypertension, Hypokalemia and Licorice

“…There is evidence that licorice consumption enhances vasoconstriction action in vascular smooth muscles via inhibition of 11 BHSD2 with subsequent alterations in endothelin-1 and nitric oxide systems ( Figure 1). Inhibition of both, renal and vascular 11 BHSD2 contributes to the development of hypertension with chronic licorice ingestion [2].…”

Cardiac hypertrophy in Cushing’s syndrome: if not hypertension then what?

“…The pathophysiology of the direct cortisol action on the cardiovascular system, albeit important, is much less comprehended, mainly due to its complexity [16]. Cortisol acts through both the glucocorticoid receptor-GR, which is ubiquitously expressed, and the mineralocorticoid receptor-MR, which is expressed in various tissues, including the myocardium, endothelial cells and the vascular smooth muscle.…”

“…Several other mechanisms include: induction of perivascular inflammation through activation of the MR, production of cytokines that may promote myocardial stiffness and contractile dysfunction by local inflammatory cells mainly the macrophages, reduced expression of eNOS and, potentiation of adrenergic action. Most of the data, however, come from ex vivo experiments or animal models making it difficult to delineate the contribution of each factor [16].…”