How does lisinopril work to lower diastolic blood pressure?

Mechanism of Action of Lisinopril for Lowering Diastolic Blood Pressure

Lisinopril lowers diastolic blood pressure primarily by inhibiting angiotensin-converting enzyme (ACE), which reduces angiotensin II formation, leading to decreased peripheral arterial resistance with little or no change in cardiac output or heart rate. 1

Primary Mechanism of Action

• Lisinopril inhibits angiotensin-converting enzyme (ACE), which blocks the conversion of angiotensin I to the potent vasoconstrictor angiotensin II 1
• Decreased angiotensin II levels lead to reduced vasopressor activity, resulting in vasodilation and decreased peripheral arterial resistance 1, 2
• The reduction in peripheral arterial resistance is the primary mechanism by which lisinopril lowers diastolic blood pressure 1
• Unlike beta-blockers or certain calcium channel blockers, lisinopril does not directly affect heart rate or cardiac output 1, 3

Secondary Mechanisms

• Inhibition of ACE also decreases aldosterone secretion from the adrenal cortex, which can lead to small increases in serum potassium 1
• ACE is identical to kininase, an enzyme that degrades bradykinin (a vasodilator peptide); inhibition of kininase may increase bradykinin levels, potentially contributing to vasodilation 1
• Lisinopril is effective in both high-renin and low-renin hypertension, suggesting multiple mechanisms of action 1, 2

Pharmacodynamic Effects

• The antihypertensive effect begins within 1-2 hours after oral administration 2
• Peak blood pressure reduction occurs around 6-8 hours after dosing 2, 4
• The effect persists for at least 24 hours, allowing for once-daily dosing 2, 4
• Lisinopril produces a smooth, gradual blood pressure reduction without affecting cardiovascular reflexes 2

Hemodynamic Effects

• In hemodynamic studies, lisinopril reduced blood pressure by decreasing peripheral arterial resistance with minimal changes to cardiac output 1
• There is little to no change in heart rate with lisinopril administration, unlike beta-blockers 1, 3
• Some studies have shown a non-significant increase in mean renal blood flow following lisinopril administration 1
• In patients with congestive heart failure, lisinopril decreases pulmonary capillary wedge pressure and systemic vascular resistance while increasing cardiac output 1

Clinical Considerations

• Lisinopril is effective in reducing both systolic and diastolic blood pressure, with reductions of 11-15% in systolic and 13-17% in diastolic pressure when used as monotherapy 2
• The addition of hydrochlorothiazide enhances the antihypertensive effect of lisinopril 2
• Lisinopril does not cause metabolic side effects such as hypokalemia, hyperglycemia, hyperuricemia, or hypercholesterolemia that are sometimes seen with diuretics 2
• The blood pressure lowering effect is consistent across different age groups but may be less effective in Black patients compared to Caucasians 1

Potential Pitfalls and Caveats

• Symptomatic postural hypotension can occur, particularly in volume and/or salt-depleted patients 1
• Renal function should be monitored, especially in patients with pre-existing renal impairment, as significant accumulation of lisinopril occurs in patients with severe renal impairment 2
• Concomitant use of NSAIDs may reduce the antihypertensive effect of lisinopril 1
• Hyperkalemia may occur, particularly in patients with renal impairment or those taking potassium-sparing diuretics or potassium supplements 1