acts in kidney, at distal nephron 8 amino acid peptide, very short t 1/2 (~ 1 minute) angiotensinogen – is precursor and is inactive renin – an enzyme makes angiotensin I ACE – makes ANGII ANGII is now an active molecule and gives you aldosterone release Juxtaglomerular Apparatus and Regulation of GFR - modification of both tubule and arteriole walls o modified tubular epithelium macula densa o modified arteriolar wall specialized smooth muscle cells called granular cells (JG cells) - granular cells are what secrete renin enzyme, its involved in salt and water balance - macula densa releases paracrine factors that act on smooth muscle of afferent arteriole
Activation of Renin-Angiotensin System - in response to LOW BP - renin from kidney initiates pathway what stimulates renin release from granulae cells of juxtaglomerular apparatus? What tells the granular cell there low pressure 1. Granular cells monitor BP in the afferent arteriole, and release renin with BP is low – local 2. Paracrine feedback from macula densa cells in distal tubule – local a. Low flow rate ^ renin release (and vice versa) 3. Sympathetic pathways originating in cardio control center in medulla terminate on granular cells – systemic a. Part of baroreceptor response to low BP 15 BP direct effect GFR NaCl transport across macula densa (distal tubule) granular cells (JGA) symp cardio control centre renin cardio control cenre cardiovascular response hypo- thalamus AVP arterioles vaso- constrict BP thirst proximal tubule aldosterone adrenal cortex Na + reabsorption volume, maintain osmolarity Fig 20.10 RAS and the Homeostatic Response to Drop in BP angiotensinogen liver ANG I ANG II ACE vascular endothelium constantly producing Drop in BP – granular cells detect it and release renin right away Drop in filtration macula densa renin release Sympathetic neurons renin release Cardio vascular response fast response, increases HR Arterioles tighten fast response Hypothalamus vasopression – save water response, give you thirst to add water Aldosterone save Na RAS and Hypertension - Blocking ANG II is a great treatment interest for hypertension o ACE inhibitors o Angiotension receptor blockers o Direct renin inhibitors
What Mechanisms oppose AVP and aldosterone? - AVP and aldosterone keep BP up and volume up by promoting conservation of water and Na reabsorption Hormones that promote loss of water and Na are - Di uresis and natri uresis, Atrial Natriuretic Peptide (ANP): - Produced in specialized myocardial cells, mostly in atria - Released when cells stretch more than normal 19 blood volume atrial stretch myocardial cells ANP hypothalamus kidney tubule afferent arteriole dilates AVP Na + reabsorption Na + & H 2 O excretion blood volume BP GFR renin aldosterone symp adrenal cortex cardio control centre Fig 20.11 Natriuretic Peptides: Oppose RAS Behavioural Mechanisms in Na and Water Balance - Replace water thirst o Sensors are in the hypothalamus, thirst is triggered by shrinkage of osmoreceptors (hyperosmolarity) o ANGII acts on hypothalamus o Drinking relieves thirst - Replacing Na: o Low Na triggers salt appetite o Linked to ANG II and aldosterone (Na balance)
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- Spring '10
- Physiology, Nephron, proximal tubule, Glomerulus