Can Steroids Cause High Blood Pressure?There is considerable evidence to support the idea that steroid hormones have the potential to increase blood symptoms low female testosterone levels that may not always be via 'classical' mineralocorticoid or glucocorticoid action. Epidemiological studies, together with the evidence from studies in animals, proposed the link between an adverse intra-uterine environment i. We tested this by treating pregnant ewes and foetuses with excess steroid early in pregnancy. The mean ages at which the prenatal exposure to glucocorticoid dexamethasone 0. Basal blood pressures and hormones and the vascular responsiveness to graded doses of angiotensin II and noradrenaline, or to a 5-day adrenocorticotropin hormone treatment Ocin lambs at 4, 10 and 19 months of age were studied. Prenatal glucocorticoid exposure did the effects of steroids on blood pressure alter vascular responsiveness to noradrenaline, angiotensin II and ACTH in these sheep at any of the ages studied.
Blood pressure--How high is to high on cycle?
Corticosteroids are key regulators of whole-body homeostasis that provide an organism with the capacity to resist environmental changes and invasion of foreign substances. The effects of corticosteroids are widespread, including profound alterations in carbohydrate, protein, and lipid metabolism, and the modulation of electrolyte and water balance. Corticosteroids affect all of the major systems of the body, including the cardiovascular, musculoskeletal, nervous, and immune systems, and play critical roles in fetal development including the maturation of the fetal lung.
Because so many systems are sensitive to corticosteroid levels, tight regulatory control is exerted on the system. The direct effects of corticosteroids are sometimes difficult to separate from their complex relationship with other hormones, in part due to the permissive action of low levels of corticosteroid on the effectiveness of other hormones, including catecholamines and glucagon.
Nevertheless, the effects of corticosteroids can be classified into two general categories: Although the following section discusses the separate effects of glucocorticoids and mineralocorticoids, it must be emphasized that natural steroids possess both glucocorticoid and mineralocorticoid activity to some extent. The ratio between the two activities ranges from all glucocorticoid and almost no mineralocorticoid activity cortisol to all mineralocorticoid and almost no glucocorticoid activity aldosterone.
Glucocorticoids stimulate the conversion of protein to carbohydrate through gluconeogenesis and promote the storage of carbohydrate as glycogen.
The increase in urinary nitrogen after an increase in glucocorticoids is the result of amino acid mobilization from protein and its subsequent breakdown as a source of carbon during gluconeogenesis. Adrenalectomized animals are able to function normally as long as food ie, free amino acids is available. Upon starvation, however, these animals cannot mobilize amino acids from muscle or serum protein, indicating that cortisol plays a role in the mobilization process. Prolonged exposure to glucocorticoids leads to a diabetic-like state due to the increase in plasma glucose, while low glucocorticoid concentrations lead to hypoglycemia, decreased glycogen stores, and hypersensitivity to insulin.
Glucocorticoids also decrease facilitated uptake of glucose in peripheral tissues to provide more glucose for glycogen formation in the liver. This effect is particularly prevalent in leukocytes and may be a major contributing factor to the rapid elevation in blood glucose after steroid administration.
The complex mechanisms for the peripheral effects of glucocorticoids are still unclear, but chronic administration can result in the atrophy of lymphatic tissue and muscle, osteoporosis, and thinning of the skin. There are two established effects of glucocorticoids on lipid metabolism.
One is the redistribution of body fat in hypercorticism; the other is facilitation of effects of lipolytic agents. Large doses of glucocorticoids lead to redistribution of fat to the upper trunk and face, with a concomitant loss of fat in the extremities.
Therefore, glucose and triglyceride accumulation would occur in response to the rise in insulin levels. Fat cells containing higher levels of receptor perhaps in the periphery would respond to the high glucocorticoid level by decreasing glucose uptake and would not accumulate triglycerides. Alternatively, cells in the extremities may be less sensitive to insulin. The major effect of mineralocorticoids is the regulation of electrolyte excretion in the kidney. Similar effects on cation transport in most other tissues account for all the systemic activity of mineralocorticoids.
The primary features of mineralocorticoid excess are positive sodium balance, increased extracellular fluid volume, normal or slightly high plasma sodium, hypokalemia, and alkalosis. Hypocorticism results in renal loss of sodium, hyponatremia, hyperkalemia, and a decrease in extracellular fluid volume and cellular hydration.
Aldosterone modulates sodium levels by activating mineralocorticoid receptors in the distal tubules of the kidney, leading to increased permeability of the apical membrane of the cells lining the cortical collecting tube. However, there is also evidence for a rapid within minutes upregulation of sodium-hydrogen exchange by aldosterone that is independent of traditional mineralocorticoid receptors.
Mineralocorticoids also increase calcium and magnesium excretion, probably due to volume expansion. The mechanism for this effect is unknown but may involve mineralocorticoid receptor downregulation and subsequent cessation of hormonal responsiveness.
Glucocorticoid effects on the kidney differ from mineralocorticoid effects. Glucocorticoids increase water diuresis, glomerular filtration rate, and renal plasma flow. Although increases in sodium retention and potassium excretion occur with cortisol, there seems to be no increase in hydrogen excretion. The major renal complications of glucocorticoid therapy are nephrocalcinosis, nephrolithiasis, and increased stone formation as a result of increased urinary calcium and uric acid.
Electrolyte changes also occur outside the kidney in response to mineralocorticoid treatment, in the gastrointestinal mucosa, 43 salivary and sweat glands, 44 and exocrine pancreas. In the intestine, aldosterone does not cause changes in intestinal electrolyte absorption, 45 but glucocorticoids increase sodium and water absorption and potassium secretion.
Both glucocorticoid and mineralocorticoid receptors are present in the mucosa, but dexamethasone can bind to both receptor types whereas aldosterone can only bind to its own receptor. Cortisol also increases gastric acid secretion and blood flow to the gastric mucosa, while decreasing the rate of gastric cell proliferation. High doses of glucocorticoids may cause peptic ulceration or aggravate preexisting ulcers.
In addition to effects on ACTH secretion, corticosteroids influence the action of several other hormones. Cortisol increases growth hormone secretion in patients with acromegaly.
This response is apparently a result of decreased maturation of the epiphyseal plates and a decrease in long bone growth. The major effects of corticosteroids on the cardiovascular system are a result of their influence on plasma volume, electrolyte retention, epinephrine synthesis, and angiotensin levels, which together result in the maintenance of normal blood pressure and cardiac output.
However, the hypotension that occurs from corticosteroid deficiency cannot be totally explained by these factors. Corticosteroids have effects on myocardial responsiveness, arteriolar tone, and capillary permeability. Hypocorticism leads to increased capillary permeability, inadequate vasomotor response, and decrease in cardiac output and cardiac size. Hypercorticism leads to chronic arterial hypertension, 55 an effect probably due to prolonged, excessive sodium retention and specific to mineralocorticoids.
Aldosterone affects ion transport in the vascular smooth muscle and the central nervous system, 56 possibly altering sympathetic output by influencing the periventricular area of the hypothalamus, where information about cardiovascular status, electrolyte and fluid balance are integrated.
Hypertension can also be induced by glucocorticoids. Although the mechanism for this response is unknown, glucocorticoids influence many factors that modulate blood pressure. For example, they increase filtration fraction and glomerular hypertension, as well as the synthesis of angiotensinogen and atrial natriuretic peptide. They decrease prostaglandin synthesis, which leads to decreased vasodilation, and simultaneously increase responsiveness to vasopressors.
They modulate vascular tone by decreasing expression of calcium-activated potassium channels, and there is evidence that glucocorticoids potentiate atherosclerosis and thromboembolic complications. Normal corticosteroid levels are required for muscle maintenance, but altered glucocorticoid or mineralocorticoid levels can lead to muscle abnormalities.
Corticosteroid insufficiency results in decreased work capacity of striated muscle, weakness, and fatigue. This response reflects an inadequacy of the circulatory system rather than electrolyte and carbohydrate imbalances. Chronic glucocorticoid administration results in induction of osteoporosis, a serious limiting factor in the clinical use of steroids. Glucocorticoid-induced bone loss is a multifaceted process. Glucocorticoids reduce bone remodeling by directly modulating osteoclast, osteoblast, and osteocyte function.
They increase renal calcium excretion and decrease gastrointestinal calcium absorption, resulting in reduced serum calcium. Reduced serum calcium causes increased secretion of parathyroid hormone PTH , and glucocorticoids increase PTH sensitivity. PTH action in turn stimulates osteoclast activity. Corticosteroids affect the nervous system indirectly in a number of ways, by maintaining normal plasma glucose levels, adequate circulation, and normal electrolyte levels.
Direct effects of corticosteroids on the central nervous system occur, but are not well defined. Corticosteroid levels influence mood, behavior, electroencephalograph patterns, memory consolidation, and brain excitability. Chronic glucocorticoid treatment causes cell death in hippocampal neurons in rats, and elevated glucocorticoid in the hippocampus is thought to play a role in altered cognition, dementia, and depression in aging humans.
Cushing disease patients sometimes develop neuroses and psychoses that are reversible with the removal of excess hormone. However, increased brain excitability induced by cortisol is not due to changes in sodium concentration. Chronic glucocorticoid treatment can also result in pseudotumor cerebri, primarily in children. Corticosteroids increase hemoglobin and red cell content of blood, possibly by retarding erythrophagocytosis.
This effect is demonstrated by the occurrence of polycythemia in Cushing disease and mild normochromic anemia in Addison disease. Corticosteroids also affect circulating white cells. Glucocorticoid treatment results in increased polymorphonuclear leukocytes in blood as a result of increased rate of entrance from marrow and a decreased rate of removal from the vascular compartment.
In contrast, the lymphocytes, eosinophils, monocytes, and basophils decrease in number after administration of glucocorticoids. Cell numbers then rise 24 to 72 h after treatment. A decrease in basophils occurs by an unknown mechanism. Glucocorticoids prevent or suppress the full inflammatory reaction to infectious, physical, or immunologic agents, inhibiting early inflammatory events such as edema, cellular exudation, fibrin deposition, capillary dilatation, migration of leukocytes into the area, and phagocytic activity.
Later events, such as capillary and fibroblast proliferation, deposition of collagen, and cicatrization, are also inhibited. The antiinflammatory mechanism of glucocorticoids, while not completely understood, is of great therapeutic relevance and is the subject of intense scientific investigation. A major effect of glucocorticoids on the inflammatory process is inhibition of recruitment of neutrophils and monocytes.
Because PLA2 is an enzyme involved in prostaglandin synthesis, glucocorticoids ultimately decrease the synthesis and release of prostaglandin mediators of cell adhesion. Glucocorticoids also inhibit synthesis of plasminogen activator and migration inhibitory factor, 69, 70 stabilize lysosomes thereby decreasing the release of hydrolytic enzymes and histamine 71 , and decrease binding of chemokines that attract white blood cells.
It is well known that hypocorticism results in hypertrophy of lymphoid tissue ie, thymus, spleen, lymph nodes and hypercorticism leads to dimunition or total loss of these tissues. Glucocorticoids induce rapid apoptosis in lymphatic tissue in rats and mice, but these effects seem to occur only at pharmacologic doses in man.
The effects seen in humans, therefore, may be due to changes in the rate of formation or destruction of lymphoid cells that become evident over a longer period of time. More acute effects of glucocorticoid on lymphoid cells in man are probably caused by sequestration of the cells rather than by cell lysis, although there is evidence that certain types of activated T lymphocytes are susceptible to glucocorticoid-induced apoptosis. Glucocorticoids decrease the secretion of interleukin 1 and other mediators of immune response, inhibit lymphocyte participation in delayed hypersensitivity reactions, and interfere with the rejection of immunologically incompatible graft tissue.
High doses of glucocorticoids inhibit immunoglobulin synthesis, kill B cells, 74 and decrease production of components of the complement system. Other effects of prolonged glucocorticoid therapy include ophthalmologic posterior subcapsular cataracts, 76 increased intraocular pressure 77 and dermatologic redistribution of subcutaneous fat, hirsutism, alopecia, impaired wound healing, purpura, purple striae, and acneiform eruptions 78 problems.
Long-term glucocorticoid treatment, with the concomitant immunosuppression, also leaves patients susceptible to invasive diseases such as Kaposi sarcoma 79 and fungal infections. By agreement with the publisher, this book is accessible by the search feature, but cannot be browsed. Turn recording back on. National Center for Biotechnology Information , U.
BC Decker ; Intermediary Metabolism Glucocorticoids stimulate the conversion of protein to carbohydrate through gluconeogenesis and promote the storage of carbohydrate as glycogen. Electrolyte and Water Balance The major effect of mineralocorticoids is the regulation of electrolyte excretion in the kidney. Endocrine System In addition to effects on ACTH secretion, corticosteroids influence the action of several other hormones.
Cardiovascular System The major effects of corticosteroids on the cardiovascular system are a result of their influence on plasma volume, electrolyte retention, epinephrine synthesis, and angiotensin levels, which together result in the maintenance of normal blood pressure and cardiac output.
Musculoskeletal System Normal corticosteroid levels are required for muscle maintenance, but altered glucocorticoid or mineralocorticoid levels can lead to muscle abnormalities.