GCs on HT Flashcards
What to the majority of patients with cushings have? Hypothesised mechanism behind this? But why is there another theory?
HT. Thought to be due to saturation of 11bHSD2 so act on the MR receptor. However, dexamethasone causes increase in BP and is selective for GR.
What do human aortic endothelial cells express? Evidence
ACTH-R and 11bHSD2. Shown by RNA PCR. ACTH inhibits 11bHSD2 and increases the amount of local cortisol available. Cell culture study, using agonist and antagonist of ACTH. More agonist, more cortisol production
What is the action of dexamethasone and AVP on 11bHSD2 mRNA in the kidney?
They both stimulate the increase of 11bSHD2 mRNA
What major cardiovascular risk factor are glucocorticoids linked to and evidence?
Atherosclerosis. Mice generated that were apo E lipoprotein deficient (highly susceptible to atherosclerosis) and given 11bHSD1 inhibitor which blocked the amount of atherosclerosis
Which type of molecule do glucocorticoids effect?
Inhibit Vasodilatory prostaglandins (in turn increases the actions of vasoconstrictors e.g. catecholamines)
Example of action on prostaglandins
Annexin 1 released from cell and has an autocrine effect, inhibits actions of phospholipase c (important for generation of prostaglandins)
How do glucocorticoids interact with the RAS? Evidence
Glucocorticoids increase hepatic and adipose tissue synthesis of angiotensinogen. Pressor responses to AT2 and noradrenaline enhanced in patients with cushings in rats and dogs. Also potentiate Ang 2 increase in IP3 production in VSMC
Another action of the glucocorticoids on the RAS. Evidence
Dex increases the amount of AT1 receptors (angiotensin 2 binds to). More receptors, more activity. Action blocked with a GR antagonist, looking at mRNA.
What is another action that glucocorticoids may have?
They may inhibit vasodilatory NO synthase. 3x20 patients on either valsartan (AT2 antagonist), diuretic or placebo and NO synthase inhibitor. Those on valsartan had decreased blood flow compared to others.
What do glucocorticoids do to another hormone? Think athletes
They increase erythropoietin that makes the blood more viscous and decreases NO synthase
What is there evidence that glucocorticoids may have a direct effect on?
Cardiac output
What is the acute effect of glucocorticoids on the catecholamines?
Acutely cortisol decreases the effects of the catecholamines. Rats stressed through immobilisation. Raised catecholamine effects were attenuated by cortisol injection. Increased conversion of noradrenalin to adrenaline through PMNt
What happens in chronic glucocorticoids to the catecholamines
Chronic glucocorticoids increase catecholamines
What are gender differences in utero?
Males tend to have increased ACTH and corticosterone in the morning and females elevated BP if exposed in utero
