Which blood pressure medications, such as Angiotensin-Converting Enzyme (ACE) inhibitors or Angiotensin Receptor Blockers (ARBs), elevate the plasma renin ratio?

Blood Pressure Medications That Elevate Plasma Renin Ratio

ACE inhibitors, ARBs (angiotensin receptor blockers), and diuretics all significantly elevate the plasma renin ratio, with ACE inhibitors and ARBs causing the most pronounced increases (20-40 fold elevations in plasma renin concentration). 1, 2, 3, 4

Mechanism of Renin Elevation

ACE Inhibitors and ARBs

• ACE inhibitors block the conversion of angiotensin I to angiotensin II, removing the negative feedback on renin secretion and causing plasma renin activity to double or triple. 2
• ARBs block the AT1 receptor, preventing angiotensin II from inhibiting renin release, which similarly causes a doubling to tripling in plasma renin activity and a consequent rise in angiotensin II plasma concentration. 1
• Both drug classes work through Gsα-dependent stimulation of adenylyl cyclase, indirectly activating the cAMP/PKA pathway to stimulate renin synthesis and release. 3

Diuretics

• Thiazide and thiazide-like diuretics (chlorthalidone, indapamide) elevate plasma renin concentration through volume depletion and activation of compensatory mechanisms. 4
• When combined with ACE inhibitors, diuretics produce additive effects on renin elevation (mean renin concentration of 54 mU/L with combination therapy vs. 41 mU/L with ACE inhibitor alone). 5

Clinical Implications for Primary Aldosteronism Screening

Beta-blockers are the most problematic medication when screening for primary aldosteronism because they suppress renin concentration, artificially elevating the aldosterone-to-renin ratio and causing false-positive results. 4

Medication Effects on Screening:

• Beta-blockers: Highly suppress renin (mean 12 mU/L vs. 17 mU/L untreated), increasing false-positive aldosterone/renin ratios. 5, 4
• Calcium channel blockers: Have no significant influence on aldosterone or renin concentrations and may be continued during screening. 4
• ACE inhibitors and ARBs: Decrease aldosterone levels only minimally and may be continued during screening, though they do elevate renin. 4
• Spironolactone: Causes renin to escape suppression and reach very high levels in primary aldosteronism patients. 4

Magnitude of Renin Elevation

• Acute administration of ACE inhibitors (captopril, quinaprilate) or ARBs (candesartan) increases plasma renin concentration 20-40 times above baseline in normal individuals. 3
• Chronic treatment with enalapril for 7 days on a low-sodium diet produces a 35-fold increase in plasma renin concentration. 3
• The renin elevation begins within one hour of ACE inhibitor administration, with peak effects at 3-4 hours. 2

Important Caveats

Beta-blocker co-administration largely prevents the renin upregulation caused by ACE inhibitors and diuretics—renin concentrations with combination therapy (21-22 mU/L) are significantly lower than with ACE inhibitors or diuretics alone (41-54 mU/L). 5

• This interaction occurs because beta-blockers suppress renin release at the juxtaglomerular apparatus level. 5
• The clinical significance is that patients on beta-blockers may not show the expected renin elevation when ACE inhibitors or ARBs are added. 5