Angiotensin Converting Enzyme (ACE) inhibitors: Mechanism of Action and Clinical Findings Angiotensin Converting Enzyme (ACE) Inhibitors
Inhibits the conversion of angiotensin I to angiotensin IIà↓ serum angiotensin II levels
Inhibits breakdown of bradykinin
↓ Activation of zona glomerulosa region of the adrenal cortex
↓ Aldosterone secretion from the adrenal cortex
↓ Expression of basolateral Na+/K+ pump
and ↓ insertion of luminal Na+ channels in principal cells of the cortical collecting duct in kidney
↓ K+ secretion into urine
↑ Serum K+ concentration
Hyperkalemia
↓ Activation of Na+/H+ exchanger in proximal convoluted tubule (PCT) of the kidney
↓ Na+ absorption into PCT and ↓ H+ excretion into lumen
↓ Na+ absorption into the blood
↓ Renal H2O reabsorption via osmosis
↓ Activation of paraventricular nuclei located in the hypothalamus
↓ Secretion of anti- diuretic hormone (ADH)
into the capillaries of the posterior pituitary gland
↓ Aquaporin channel insertion at cortical collecting duct in kidney
↓ Renal H2O reabsorption
à↑ serum bradykinin levels Vasodilation of efferent
arteriole in kidneys
↓ Hydrostatic pressure within the glomerular capillaries
↑ Activation of cyclooxygenase-2 pathway
↑ Prostaglandin production
↓ Activation of angiotensin II type 1 receptors on surface of arteriolar smooth muscle
↓ Activity of G protein-coupled receptor intracellular secondary messenger cascade
↓ Systemic arteriolar vasoconstriction
↓ Total peripheral resistance (resistance
to blood flow by systemic vasculature)
↓ Blood Pressure
↓ total blood flow perfusing kidneys
Renal hypoxia
↑ Systemic arteriolar vasodilation
↓ Total peripheral resistance
↓ Blood Pressure
↓ Concentration of protein
travelling through tubules for excretion
↓ Fraction of H2O filtered from glomerular capillaries into bowman’s capsule (start of the renal tubule)
↓ Filtration of blood contents through glomerular membranes
Sensitization of airway vagal afferent receptors
Stimulation of the cough
center located in the medulla oblongata
Cough
↓ Protein in urine
High K+ levels surrounding the heart muscle cellsàchronic depolarization
of the cardiomyocyte cell membrane àalters cardiomyocyte conduction (complex mechanisms)
Cardiac Arrythmias (see relevant slide on Hyperkalemia: Clinical Findings)
↓ Effective arterial blood volume
Authors:
Nicole Brockman Reviewers:
Emily Wildman, Austin Laing Adam Bass*, Yan Yu*
* MD at time of publication
Renal tubules have relatively less water compared with the peritubular capillaries
↓ H2O reabsorption from the renal tubule back into the blood
↑ Serum creatinine, ↓ estimated glomerular filtration rate
Renal nephron injury and dysfunction
Acute Kidney Injury
(rise in creatinine >26.5umol/L in <7 days) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 10, 2022 on www.thecalgaryguide.com