Pharmacology for Anaesthesia and Intensive Care

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Antihypertensives

Drugs affecting the renin–angiotensin–aldosterone system


Adrenergic neurone blockade


Centrally acting


Ganglion blockade


Diuretics


Adrenoceptor antagonists


Ca2+channel antagonists

Renin–angiotensin–aldosterone system

Physiology

The juxtaglomerular apparatus within the kidney consists of three distinct cell

types:


Juxtaglomerular cells form part of the afferent arteriole as it enters the glomerulus

and are supplied by sympathetic nerves. They contain prorenin, which is converted

to the acid protease renin before systemic release.


The macula densa is a region of cells at the start of the distal convoluted

tubule, which lie adjacent to the juxtaglomerular cells of the same nephron.


Agranular lacis cells, which lie between the afferent and efferent arterioles adjacent

to the glomerulus.

Under the following conditions the juxtaglomerular apparatus will cause the release

of renin into the circulation:


Reduced renal perfusion


Reduced Na+at the macula densa


Stimulation of the renal sympathetic fibres viaβ 1 -adrenoceptors

Renin (half-life 80 minutes) splits the decapeptide angiotensin I from the cir-

culating plasma protein angiotensinogen, which is synthesized in the liver and

is present in theα 2 -globulin fraction of plasma proteins. Angiotensin-converting

enzyme (ACE) converts angiotensin I to the active octapeptide angiotensin II, and

also inactivates bradykinin. Angiotensin II is broken down in the kidney and liver

to inactive metabolites and angiotensin III, which retains some activity (Figure

16.1).