Aldosterone: Effects and Regulation

00:01 How this process is controlled is interesting.

00:05 Before we go through that, let's also discuss how if you give someone a drug such as aldosterone, what happens to the overall response of sodium, chloride, and potassium.

00:19 So we have baseline levels and these are urinary excretion rates of sodium.

00:26 When aldosterone is given, you see a dramatic reduction in the urinary excretion of sodium.

00:33 If there is a reduction in the urinary excretion that means it's being reabsorbed.

00:38 Once you remove aldosterone, it recovers.

00:43 If you look at urinary chloride concentration, if you think about having a nice, stable baseline level, once you give out aldosterone, you again see a decrease in chloride excretion.

00:56 Then this recovers again.

01:00 Potassium is interesting in that you have basal levels, but once you give out aldosterone you see a secretion of potassium.

01:11 So unlike sodium and chloride which are both reabsorbed to a greater degree with aldosterone, potassium is secreted.

01:19 So let's walk through the mechanism by which how aldosterone does this particular action.

01:25 The first thing to think about is where aldosterone comes from.

01:29 Aldosterone is part of the renin angiotensin aldosterone system and it responds to low blood pressure than blood volumes which result in low renal blood flows which increases renin, angiotensin I, angiotensin II is increased and then that will increase aldosterone levels.

01:50 The second mechanism by which aldosterone can increase is by having high levels of potassium, so if you're hyperkalemic.

02:01 So either angiotensin II or hyperkalemia both will stimulate the aldosterone release.

02:07 What does the aldosterone do at the level of the kidney? Aldosterone is a steroid hormone.

02:14 So aldosterone can move through the basal lateral membrane because it's lipophilic.

02:19 It binds to a cytosolic receptor known as mineralocorticoid receptor.

02:25 This particular receptor once bound to aldosterone translocates into the nucleus of the cell.

02:31 Transciption and translation occur in which you are going to produce 3 different proteins.

02:38 One is the ENaC sodium channel; the second is the ROMK potassium channel; and the third is the sodium potassium ATPase.

02:47 These are then expressed, both the ENaC sodium channel and the ROMK channel, on the apical membrane, and the sodium potassium ATPase on the basolateral membrane.

02:58 That sodium potassium ATPase on the basolateral membrane pumps out sodium and potassium allows to travel into the cytosol.

03:08 The potassium that travels into the cytosol is then removed across the apical membrane by those ROMK channels.

03:15 The ENaC sodium channel allows for the reabsorption of sodium.

03:19 That is why you see when we have aldosterone being given, that there is a decrease in the sodium excretion as measured in the urine, and there's an increase in potassium secretion as measured in the urine.

03:35 And that is all driven by the placing of these two channels in the apical membrane with aldosterone infusion.

03:43 That is done from this whole mineralocorticoid receptor increasing transcription translation of these proteins.

03:51 The next particular hormone that we need to deal with is something called arginine vasopressin.

03:56 So arginine vasopressin also known as antidiuretic hormone, only really works in the collecting tubules and the collecting duct.

04:07 And that can be seen in this particular diagram here, where the only areas of reabsorption that occur are the ones in green.

04:16 So those last two, the cortical collecting duct and the inner medullary collecting duct, are the two places that have these green bars, meaning that when arginine vasopressin is given or antidiuretic hormone, you get more reabsorption of water.

04:32 What are the mechanisms of action for arginine vasopressin? They will bind to a receptor that's located on the basolateral membrane.

04:41 These receptors are known as V2 receptors.

04:44 They are G-coupled protein receptors that stimulate adenylate cyclase which then increase cyclic AMP.

04:52 The cyclic AMP then goes through a phosphorylation cascade that involves protein kinase A and other protein phosphorylation.

05:01 This protein phosphorylation will stimulate, there to be an increase in transcription, translation of various protein that are associated with arginine vasopressin Mechanisms of action as well as the receptor subtypes.

05:18 It also stimulates the vesicles that have specialized water transporter known as aquaporin to move from a vesicle within the cytosol, it will dock, and fuse, and merge on the apical membrane.

05:35 These particular aquaporin channels are known as aquaporin2 channels.

05:40 So you have V2 receptors and aquaporin2 channels.

05:46 If you have an aquaporin present in the apical membrane of the inner medullary duct cells or the cortical collecting tubules, water will allow to transport across the apical membrane.

05:58 How do you remove these aquaporins ? These are endocytosed when arginine vasopressin levels are low.