Nursing Pharmacology Chapter 24: Vasoactive Peptides
Angiotensin II receptors are widely distributed
Plasma membrane localization enable rapid onset of effects
At least two major receptor subtypes
AT1 , which exhibits high losartin (receptor blocker) affinity
Equal affinity for saralasin and angiotensin II
Predominates at vascular smooth muscle
Vascular smooth muscle: G- protein coupled system
Receptor activation at vascular smooth muscle:
Phospholipase C -mediated production of inositol triphosphate IP3 and diacylglycerol (DAG)
Activation of IP3, DAG cascade: DAG may activate smooth muscle Ca2+ channels; IP3 releases Ca2+ from endoplasmic and sarcoplasmic reticulum
Smooth muscle contraction
Non-G protein coupled system at other sites
AT2, by contrast exhibits low losartin affinity
Equal affinity for saralasin and angiotensin II
Clonidine (Catapres)
Mechanism of Action:
Decrease in CNS-mediated renal stimulation
Direct intra-renal effect
Methyldopa (Aldomet)
Propranolol (Inderal) (and other β-adrenergic receptor blockers)
Mechanism of Action:
Blockade of renal β-adrenergic receptors
Orally active (unapproved) renin inhibitors:
Remikiren
Enalkiren
Poor bioavailability
Poor absorption
First-pass effect
Increased plasma renin levels: interrupts angiotensin II negative feedback effect on renin secretion.
Converting Enzyme Inhibitors (ACE)
Examples: Captopril (Capoten), Enalapril (Vasotec)
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Angiotensin Converting Enzyme Inhibitors |
Trade Names |
Benazepril |
Lotensin |
Captopril |
Capoten |
Enalapril |
Vasotec |
Fosinopril |
Monopril |
Lisinopril |
Prinivil |
Moexipril |
Univasc |
Perindopril |
Aceon |
Quinapril |
Accupril |
Ramipril |
Altace |
Trandolapril |
Mavik |
Conversion blockade: angiotensin I to angiotensin II
Degradation blockade
Bradykinin (important in ACE inhibitors hypotensive effects)
Reduced bradykinin degradation: responsible for certain adverse effects-- cough, angioedema.
Substance P
Enkephalins
Management of hypertension
Management of congestive heart failure
May reduce renal vascular injury in diabetic patients
Saralasin -- antagonist
Some agonist activity
IV administration only
Less effective in lowering blood pressure compared to ACE inhibitors because:
Partial agonist properties
ACE inhibitors enhance bradykinin vasodilation
Angiotensin-II Receptor Blockers
Angiotensin II Receptor Antagonist
Trade Name
Candesartan
Atacand
Eprosartan
Teveten
Irbesartan
Avapro
Losartan
Cozaar
Olmesartan
Benicar
Telmisartan
Micardis
Valsartan
Diovan
Competitive antagonist at AT1 receptors
Effective orally
Antihypertensive effects comparable to those obtained with enalapril (ACE inhibitor)
No agonist activity
Clinical uses: Receptor Blockers
Hypertension
Congestive heart failure
Reid, I.A., Vasoactive Peptides, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 287-303.