The interaction between L-Arginine and antihypertensive drugs

L-arginine serves as a precursor for nitric oxide (NO) synthesis in the body. NO can relax vascular smooth muscle and reduce peripheral vascular resistance, thereby exerting an adjuvant antihypertensive effect. Clinical commonly used antihypertensive drugs (such as calcium channel blockers, ACEI/ARB agents, diuretics, etc.) also regulate vascular tone and blood volume through various mechanisms. The combined use of L-arginine and these drugs may produce a synergistic antihypertensive effect, while also carrying potential risks of adverse reactions. Scientific clinical management is required to maximize benefits and minimize risks.

I. Interaction Mechanisms and Effects Between L-arginine and Different Types of Antihypertensive Drugs

Interaction with ACEI/ARB AgentsRepresentative drugs: Captopril, Enalapril (ACEI); Losartan, Valsartan (ARB)

Mechanistic synergy:

ACEI/ARB agents reduce vasoconstriction by inhibiting angiotensin production or blocking its receptors. L-arginine enhances vasodilation by supplementing substrates for NO synthesis. The two work together to reduce peripheral resistance through two dimensions—"reducing constriction" and "enhancing dilation"—yielding a significant synergistic antihypertensive effect.

Potential risks:

Combined use may cause an excessive decrease in blood pressure, leading to hypotensive symptoms (dizziness, fatigue, orthostatic hypotension). Some patients may experience adverse reactions such as headache, facial flushing, and tachycardia due to excessive NO production.

Interaction with Calcium Channel Blockers (CCB)Representative drugs: Nifedipine, Amlodipine, Felodipine

Mechanistic synergy:

CCBs inhibit calcium influx to dilate blood vessels by blocking calcium channels in vascular smooth muscle. NO generated from L-arginine can activate guanylate cyclase in smooth muscle cells, further promoting calcium efflux and enhancing vasodilation. The combination improves antihypertensive efficacy, making it particularly suitable for patients with refractory hypertension.

Potential risks:

Excessive co-administration may induce reflex tachycardia, increase myocardial oxygen consumption, and potentially trigger angina pectoris in patients with coronary heart disease. Meanwhile, the risk of hypotension is higher than that of monotherapy.

Interaction with DiureticsRepresentative drugs: Hydrochlorothiazide, Spironolactone, Furosemide

Mechanisms and effects:

Diuretics lower blood pressure by sodium excretion and diuresis to reduce blood volume. Their mechanism does not directly antagonize the vasodilatory effect of L-arginine, but electrolyte and blood volume balance must be monitored during combined use:

Thiazide diuretics may cause hypokalemia, while L-arginine has little impact on serum potassium during metabolism. Potassium levels should be monitored during co-administration to avoid exacerbation of hypokalemia.

Potent diuretics (e.g., furosemide) are prone to causing hypovolemia. In such cases, combined use with L-arginine may significantly increase the risk of hypotension due to the combined effects of vasodilation and reduced blood volume.

Interaction with β-blockersRepresentative drugs: Metoprolol, Bisoprolol

Characteristics of effects:

β-blockers lower blood pressure by slowing heart rate and reducing myocardial contractility, which has weak complementarity with the vasodilatory mechanism of L-arginine. The combined use yields limited improvement in antihypertensive efficacy, but it can alleviate L-arginine-induced tachycardia (offset by the negative chronotropic effect of β-blockers), resulting in high overall safety.

II. Clinical Management Strategies

Pre-administration Assessment and Contraindication Screening

Population selection for suitability:

The combined regimen is preferentially recommended for patients with mild-to-moderate hypertension and those with refractory hypertension (poor response to monotherapy). It is particularly suitable for hypertensive patients complicated with coronary heart disease or peripheral vascular disease (NO can improve vascular endothelial function and delay atherosclerosis).

Contraindicated and cautious populations:

Absolute contraindications: Patients with severe hypotension, shock, or hypersensitivity to L-arginine.

Cautious use populations: Patients with hepatic or renal insufficiency (metabolites of arginine are excreted via the liver and kidneys), patients with heart failure (excessive blood pressure reduction may affect cardiac output), and patients with bleeding tendency (NO inhibits platelet aggregation, increasing bleeding risk).

Dosage and Combination Regimen Optimization

Recommended dosage of L-arginine:

For adjuvant antihypertensive use, the daily dosage should be controlled at 5–10 g, administered orally in 2–3 divided doses. Single high-dose intake (> 20 g) should be avoided. High-dose intravenous infusion is not recommended (intravenous infusion can rapidly increase NO levels, leading to severe hypotension).

Combination principles:

For initial combination therapy, the dosage of antihypertensive drugs should be reduced (e.g., halving the dose of ACEI/ARB agents). Blood pressure should be monitored for 1–2 weeks before gradual dosage adjustment to avoid abrupt hypotension.

Long-acting antihypertensive drugs (e.g., amlodipine, valsartan) are preferred for combination with L-arginine to maintain stable blood pressure and reduce the risk of hypotensive fluctuations.

Monitoring Protocol During Administration

Core monitoring indicators:

Blood pressure monitoring: Measure fasting morning blood pressure and bedtime blood pressure daily. The target blood pressure should be controlled below 130/80 mmHg, with systolic blood pressure not less than 90 mmHg. If hypotensive symptoms such as dizziness or syncope occur, discontinue medication immediately and seek medical attention.

Adverse reaction monitoring: Observe for NO excess-related reactions such as headache, facial flushing, and tachycardia, as well as serum potassium and creatinine levels (especially when combined with ACEI/ARB agents or diuretics).

Special population monitoring: Electrocardiogram monitoring is required for patients with coronary heart disease to avoid myocardial ischemia induced by tachycardia. Patients with hepatic or renal insufficiency should undergo regular liver and kidney function tests to adjust medication dosage.

Principles of Discontinuation and AdjustmentIf persistent hypotension or severe adverse reactions occur after combination use, L-arginine should be discontinued first to observe whether blood pressure rises; the dosage of antihypertensive drugs should not be adjusted immediately to avoid blood pressure rebound caused by abrupt reduction of antihypertensive agents.

For hypertensive patients requiring long-term L-arginine supplementation, vascular endothelial function should be evaluated every 3 months (e.g., measuring serum NO levels, brachial artery flow-mediated dilation), and dosage adjustment or discontinuation should be made based on the evaluation results.

III. Precautions

Avoid blind combination: L-arginine is only used as an adjuvant therapy for hypertension and cannot replace the core therapeutic role of antihypertensive drugs. Patients should use it under the guidance of physicians and are prohibited from increasing the dosage or combining it with other drugs without authorization.

Medication in special populations: L-arginine should be used with caution in patients with gestational hypertension and pediatric hypertensive patients, as safety data related to combination use are currently insufficient. Elderly patients, due to poor vascular elasticity and weak blood pressure regulation ability, should start with the minimum dose.

Drug-diet synergy: During L-arginine supplementation, appropriate intake of foods rich in vitamin C and vitamin E (e.g., fresh fruits and vegetables) is recommended. These vitamins can protect NO from oxidation and enhance its vasodilatory effect.