Renin-angiotensin system

What is the mechanism behind aldosterone release?

Blood pressure low --> stretch receptors stimulate adrenal gland to release aldosterone --> increases Na+ reabsorption from urine, sweat, gut --> increases osmolarity in the extracellular fluid --> increased water retention --> blood pressure returns to normal.

How are angiotensin peptides formed? What is the rate limiting step?

renin is the rate limiting step

What cells release renin? Where are the cells located?

JG cells (granular cells) located in the afferent arterioles of the glomerulus act as intra-renal pressure sensor

What stimulates renin release?

Low BP, blood volume and Na depletion - very important for Na regulation it can actually make you crave salt

When do JG cells secrete renin?

Lowered pressure -->secretion of renin (to increase systemic blood pressure via the renin-angiotensin system

What are the functions of the renin-angiotensin system?

Major role in cardiovascular (blood pressure) and body fluid homeostasis through actions of circulating angiotensin II on its various target organs: 1) adrenal cortex 2) kidney (complex effects 3) cardiovascular system 4) peripheral ANS 5) CNS 6) cell growth

What does Angiotensin converting enzyme (ACE) do? Is this enzyme specific or non-specific for angiotensin? Where is the highest concentration of ACE?

*Nonspecific enzyme* - cleaves dipeptides from diverse substrates (e.g. bradykinin, syn.: "kininase II"), dipeptidyl carboxypeptidase. Ectoenzyme (lumen) of endothelial cells, converts angiotensin I to angiotensin II (lung). Preferred substrate: not proline as penultimate amino acid at the carboxyterminus --> does not further process angiotensin II Highest concentration = lungs

What is renin secretion controlled by?

- reduced renal perfusion pressure (intrarenal stretch receptor) - reduction of sodium concentration in early distal tubule - sympathetic activation of beta-adrenergic receptors (transmitters: epinephrine, norepinephrine)

What is the role of RAAS in the kidney?

1) Antidiuresis & antinatriuresis by promoting sodium reabsorption by kidney 2) Reduced glomerular filtration

What is the role of RASS in the cardiovascular system?

1) Direct vasoconstrictor action on vascular smooth muscle (augmented by sympathetic nerve system, see (D.)) 2) Increases cardiac contractility with little change in heart rate. 3) Renin-Angiotensin System appears to play a major role in the pathogenesis of hypertension, even when plasma renin activity is not elevated (see (D.)

What is the role of the renin-angiotensin system in adrenal cortex?

1) Stimulates synthesis & release of aldosterone from zzona glomerulosa cells 2) Action augmented by hyponatremia & hyperkalemia

What is the role of RAAS in the peripheral ANS?

1) Sympathetic nervous system a) Release of norepinephrine from postganglionic neurons b) Enhanced sensitivity of target tissues to norepinephrine 2) Adrenal Medulla: release of catecholamines from chromaffin cells.

Does angiotensin I have much biological activity? WHat about angiotensin II?

Angiotensin I: very little biological activity Angiotensin II: most active form (after ACE works on angiotensin I), structure-activity relationships:

What is the role of RAAS in cell growth?

Angiotensin II mitogenic for vascular & cardiac muscle cells, may contribute to cardiovascular hypertrophy.

What is the half life of angiotensin 2 and 3? How is it mostly destroyed? What removes angiotensin from circulation ?

Angiotensin half-life: ~15-60 seconds; mostly destroyed by single passage through the pulmonary vascular bed Rapid removal from circulation by variety of peptidases (collectively "angiotensinases"): - Aminopeptidases - Endopeptidases Enzymes not specific to angiotensin

What is the role of RAAS in the CNS?

Circulating angiotensin II: can get access to brain regions lacking a blood brain barrier and may be produced within the brain 1) Physiological: Central pressor response resulting from sympathetic activation 2) Endocrine: release of ADH (vasopressin) and ACTH 3) Behavioral: thirst (dipsogenic effect) and sodium appetite

What are some things that the renin-angiostensin system have an effect on?

Hypertension Congestive heart failure Myocardial infarction Diabetic neuropathy

What is aldosterone synthesis stimulated by?

Increased angiotensin II, ACTH, or high K+ and low Na+ Acidosis Atrial stretch receptors

Does angiotensin 2 or 3 have a higher receptor affinity?

Receptor affinity for angiotensin II > angiotensin III *Angiotensin III* is as potent in some systems, e.g. aldosterone release However, in other tissues it is much less potent, e.g. vascular smooth muscle

What type of hormone is aldosterone? What produces it? What does it do?

Steroid hormone produced by outer-section (zona glomerulosa) of *adrenal cortex* in the adrenal gland Regulates blood Na+ and K+ balance

What does the RAAS system do?

The renin-angiotensin system plays a major role in cardiovascular (blood pressure) and body fluid homeostasis through actions of circulating angiotensin II on its various target organs.

Where is angiotensinogen found? Where is angiotensinogen primarily synthesized?

abundant protein in plasma Angiotensin I is cleaved from the N-terminus initially as a decapeptide Primarily synthesized in liver but also found elsewhere.

What forms of angiotensin are full agonists?

angiotensin 2 and 3

What does aspartylprotease do?

generates angiotensin I from circulating substrate, angiotensinogen

What is RAAS targeted pharmacologically to treat?

hypertension

What is the main source of renin?

kidney Plasma concentration of renin is the rate limiting factor in angiotensin II formation