2004B12 Briefly describe the secretion and functions of renin and angiotensin.

 

List:

·         Intro

·         Angiotensinogen

·         Renin

·         Angiotensin 2

·         Other angiotensins

·         Aldosterone

 

Intro:

Pathway

·  Note negative feedback

o Direct: AT2 binds AGTR1 on granular cell -> ↑Ca2+ -> ↓renin release

o Physiological: AT2 and aldosterone inhibit release of renin

Overall function

·  Essential for fluid and electrolyte homeostasis and response to haemorrhage

·  Angiotensin 2: ↑ECF volume, ↑blood pressure

·  Aldosterone: ↑ECF [Na+] and osmolality, ↑ECF:ICF ratio

 

Angiotensinogen:

Source

·  Large protein

·  Synthesised by the liver

Function

·  Relatively inert circulating precursor for angiotensin 1

 

Renin:

Source

·  Juxtaglomerular cell of the afferent arteriole

Release stimuli

·  ↓Afferent arteriolar stretch

·  β1 agonism at JG cell

·  Low NaCl load to macula densa -> ↓adenosine + ↑PGE2

Kinetics

·  Released into circulation almost immediately upon stimulus

·  Duration 30-60 mins

·  Note it is the rate limiting factor due to constitutive presence of circulating angiotensinogen and pulmonary ACE

Function

·  Enzymatic cleavage of antiotensinogen

·  Not itself vasoactive

 

Angiotensin 2:

Kinetics

·  Produced within minutes of stimulus

·  Duration 1-2 mins (but more produced if renin present)

·  Metabolised by peptidases

Cellular effect

·  Peptide hormone, 8 amino acids (angiotensin 1 is 10 amino acids)

·  Binds AT2R (Gq G-protein coupled receptor)

·  ↑IP3-> ↑ICF Ca2+; ↑DAG

Vascular effect

·  Constriction of efferent > afferent arteriole

o ↑GFP -> ↑GFR

o ↓Peritubular capillary hydrostatic pressure -> ↑reabsorption

·  Generalised vasoconstriction >> venoconstriction, ↑SVR, ↑mAP

Renal tubular effect

·  ↑Na+/H+ exchange in proximal tubule -> ↑Na+/H2O/HCO3- reabsorption -> ↑ECF volume and pH

CNS effect

·  Hypothalamus: ↑ADH release

·  Circumventricular organs: thirst -> ↑H2O and NaCl consumption

 

Other angiotensins:

AT3

·  Same as AT2 on aldosterone secretion

·  Same as AT2 at glomerulus

·  60% of AT2’s systemic vasoconstriction

AT1, AT4

·  Also less active than AT2

 

Aldosterone:

Source

·  Zona glomerulosa of adrenal cortex

·  Derivative of cholesterol

Release stimuli

·  CRH -> ACTH -> aldosterone (necessary for synthesis, minor effect on release)

·  Angiotensin 2 (major)

·  Hyperkalaemia (minor)

Cellular effect

·  Steroid hormone

·  Binds cytosolic mineralocorticoid receptor, a nuclear transcription factor

·  Increases or decreases gene expression

Renal tubular effect

·  Location: connecting tubule, collecting duct

·  Principal cell:

o ↑Na+K+ATPase synthesis and activity

o ↑Apical ANaC and ROMK activity

·  Type 1 intercalated cell:

o ↑H+ATPase activity

·  Direct effects:

o ↑ECF [Na+] and tonicity

o ↑ECF pH

o ↓ECF [K+]

·  Indirect effects:

o ↑ECF:ICF volume ratio (due to osmosis)

o ↑ADH release (due to hypertonicity)

Colon and sweat glands

·  ↑Na+K+ATPase synthesis and activity -> ↑ENaC activity

·  ↑ECF [Na+] and tonicity

 

 

 

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