Renin-Angiotensin System Pharmacology Flashcards
Renin-Angiotensin System
Angiotensinogen ***converted by renin*** Angtiotensin I ***Converted by ACE*** Angiotensin II
-Leads to: vasoconstriction sympathetic activation aldosterone secretion ***which all lead to blood pressure regulation
Juxtaglomerular Apparatus
Renin containing cells
Sympathetic Nerves
Afferent arteriole
Macula Densa
Specialized epithelial cell distal tubule
Intrarenal baroreceptor
Sense Stretch/renal perfusion pressure
What do the intrarenal baroreceptors signal when they sense low blood pressure
increased renin release so that more Na and water are held onto, which increases blood pressure
What happens when the macula densa senses a low Na load
they signla increased renin release
How does the sympathetic nervous system signal renin release
-increased renal sympathetic tone activated the B1 adrenergic receptors on JGCs this causes renin release
Exaplin how the macula densa is in involved in juxtaglomerular cell signaling to increase renin release
- decreased Na transport to the apical macula densa
- increases COX2 which produces PGs that activate adenylate cyclase in the juxtaglomerular cell and lead to increased cAMP which increases renin release
- Increases Renin
Explain how the Increased Angiotensin II leads to decreased renin
Angiotensin II binds to and activates an AT1 receptor on the juxtaglomerular cell. This activates PLC which uses PK-C as a second messenger to inhibit renin release
Where n the body does Angiotensin II activate its receptor and what is the receptor
Angiotensin II activates AT1 receptors on renal vascular smooth muscle to reduce renal blood flow
How does Angiotensin II influence GFR
It slightly reduces it
-
What does Aldosterone do
It activates the expression of target genes responsible for N and K transport
In kidneys Aldosterone increases Na and water reabsorption and increases secretion of K and H into urine
it also causes fibrosis and hypertrophy in the heart
What three things does Angiotensin II lead to
when it binds to the AT1 receptor it leads to
- vasoconstriction
- cell growth
- Aldosterone production
What does Angiotensin II do to the heart
hypertrophy of cardiac myocytes
How is Angiotensin II involved in hypertension
It leads to Na and water reabsorption which increases blood pressure. SO
If you inhibit production of Angiotensin II then you will have lower blood pressure
Losartan
AT1 receptor blocker: Competitive angiotensin receptor antagonist. Selective for the AT1
receptor subtype.
*Doesn’t let Angiotensin II bind to its receptor and elicit its effects
-decreased aldosterone secretion
-decreased vasoconstrictio
-decreased sympathetic activation
-All of this leads to decreased blood pressure
-makes more Angiotensin II bind to the AT2 receptors which leads to vasodilation, antiproliferation and apoptosis
Renin-Angiotensin System Inhibitors
- drugs that inhibit RAS by different mechanisms
- blood pressure lowering related to plasma renin activity
- Vasodilation arterial (dominant) and venous circulations
- decrease blood pressure with no change in heart rate
- can cause hypotension or hyperkalemia
- contraindicated in preganancy-fetal wasting
What is a side effect that you have to be really careful about when someone is taking a RAS drug
K!!! they could get hyperkalemia
How long does it take for a person taking Losartan to have effects on their blood pressure after administration of the first dose
6 weeks
List the Angiotensin Converting Enzyme Inhibitors
Captopril
Enalapril
Lisinopril
Captopril
ACE Inhibitor
Enalapril
ACE Inhibitor
Lisinopril
ACE Inhibitor
