Hormones and Hypertension

Abstract

The importance of changes in hormone secretion in human hypertension is a complex problem and too large to be dealt with in uniform detail in a short review. The subject encompasses not only the effects on blood pressure of primary endocrine disorders but also hormonal changes secondary to increased blood pressure. Some aspects are more fully understood than others and have been the subjects of relatively recent detailed reviews. Where this is the case, the current review has summarized the present position and cited reviews and key papers, in order to reserve space for more controversial and less well understood conditions such as the hypertension of growth hormone, thyroid hormone or glucocorticoid excess. CORTICOSTEROIDSThe human adrenal cortex synthesizes and secretes a large number of steroid hormones, biosynthetically interrelated with each other and with qualitatively and quantitatively different biological activities. The two major categories of compound are the adrenal androgens (androstenedione, dehydroepiandrosterone and testosterone) which, as far as is known, are not important in blood pressure control and will not be considered further (although there exist experimental models of hypertension which may be androgendependent), and the corticosteroids. These C21 steroids of the pregnane series exert two main types of action, mineralocorticoid and glucocorticoid effects, and excess secretion of either has widespread repercussions, particularly for neuromuscular function and the control of salt and water metabolism. Mineralocorticoids act mainly on the distal nephron via specific receptor activation to promote sodium reabsorption (with associated changes in extracellular fluid and plasma volume) and increased potassium and proton excretion, so that excess activity is characterized by hypokalaemia and a metabolic alkalosis. Aldosterone is the major mineralocorticoid in man but deoxycorticosterone (DOC) and corticosterone also have significant activity. More recently discovered compounds-18-hydroxy DOC, 18-oxocortisol and several compounds modified at position 19 (19-hydroxy or 19-nor)-may also contribute to the total mineralocorticoid action of the adrenocortical secretion (see review by Fraser & Padfield, 1985). Cortisol is the major human glucocorticoid. Glucocorticoids promote liver glycogen and protein synthesis but are catabolic in most other tissues, increasing lipolysis and protein R. Fraser et al.breakdown and reducing glucose uptake from the circulation. However, the kidney also possesses specific glucocorticoid receptors and, under experimental conditions, glucocorticoids can be shown to promote both natriuresis and kaliuresis, at least partly by raising glomerular filtration rate (GFR) and also to modulate Na+-H+ exchange in the proximal nephron (Davis & Howell, 1953;Mahnensmith & Aronson, 1985; Kinsella et al., 1985). Excess of either mineralocorticoid or glucocorticoid activity is associated with hypertension.The control of adrenocortical function is similarly complex and the subject of sev...

Expression of 11beta-hydroxylase and aldosterone synthase genes in the rat brain

“…Both aldosterone and cortisol (or corticosterone) have important effects on electrolyte balance and blood pressure by their actions on the kidney and the vasculature (Fraser et al 1989). In addition to these systemic effects, however, it is clear that they exert significant central effects.…”

BclI glucocorticoid receptor polymorphism in relation to cardiovascular variables: the Hoorn and CODAM studies

“…increased gluconeogenesis, insulin resistance, and lipolysis), glucocorticoids have a role in the complex interplay between pro-and anti-inflammatory pathways (1) and exert multiple vascular effects. Glucocorticoids increase blood pressure by enhancing sensitivity of vascular smooth muscle to catecholamines and angiotensin II, by increasing angiotensinogen synthesis, by reducing nitric oxidemediated endothelial dilatation and by sodium retention in the distal nephron (2,3). Consequently, chronic exposure to high doses of endogenous or exogenous glucocorticoids often results in an unfavorable metabolic profile and cardiovascular disease (CVD) (4,5,6,7).…”

Aldosterone-producing adenoma without hypertension: a report of two cases

“…In patient #1 this central response to aldosterone could have been modified by long-term treatment with glucocorticoids, although prednisone, used in this patient, has a very low affinity for MR (22). Moreover, excess glucocorticoids usually have a hypertensive action (23). DXM-sensitive hyperaldosteronism was also considered in both patients because recent data have shown that carriers of chimerism of the 11-beta-hydroxylase/ aldosterone synthase gene have a broad range of phenotypes and do not necessarily have arterial hypertension.…”