Sunday, December 16, 2012

ACE inhibitors, prostaglandins and the renin angiotensin system

Greetings everyone!

What are ACE inhibitors?
They inhibit angiotensin converting enzyme which converts angiotensin 1 to angiotensin 2

ACE inhibitors
Normally, the amount of renin in plasma acts as a limiting factor for angiotensin 2 generation
[Renin? Renin converts angiotensinogen to angiotensin 1]

This is why, ACE inhibitors enhance renin release
Changes that lower blood pressure or volume of decrease Na+ content release renin by three pathways-
The intrarenal baroreceptor pathway: The decreased tension in the afferent glomerular arterioles is sensed and is possibly increasing the local production of prostaglandins
The macula densa pathway: Low Na+ concentration in the tubular fluid is sensed by the macula densa cells
This induces the synthesis of COX 2 and neural nitric oxide synthase which is causes release of PGE2 and PGI2
Released prostaglandins act on the juxtaglomerular cells to promote renin secretion
Beta adrenoceptor pathway: Baroreceptor and other reflexes increase sympathetic impulses to the JG [Juxtaglomerular] cells activated through the beta1 receptors

So, beta blockers and other sympatholytics will decrease renin release
NSAIDs decrease renin release by inhibiting prostaglandin production

ACE inhibitors also inhibit an enzyme (kininase) responsible for the degradation of bradykinin
Prostaglandin synthesis is enhanced by kinins
This maybe responsible for cough and angioedema in susceptible individuals

So that is why, for the treatment of ACE inhibitor associated cough, which is prostaglandin mediated, indomethacin and other NSAIDs can be used
Another cool fact I found out is that you can use nifedipine, a calcium channel blocker, for the same :O
Usually, ACE inhibitors are substituted with angiotensin antagonists like Losartan since they do not interfere with the degradation of bradykinin and adverse effects like cough are not encountered

That's all!
I always have a tough time recalling role of prostaglandins when in comes to the renin angiotensin pathway..
So I blogged whatever I knew =D

Random cool fact:
Rennin is a milk-coagulating enzyme
found in the gastric juice of the fourth stomach of young ruminants, used in making cheese. It is also known as chymosin
This is why, some cheese packets have the non vegetarian label
It's because of the enzyme used in the production of cheese obtained from animals
Note the difference in the spellings :)



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