Does hydralazine cause bradycardia (abnormally slow heart rate)?

From the Guidelines

Hydralazine does not typically cause bradycardia, but rather tends to cause reflex tachycardia due to its vasodilatory effects. Hydralazine is a direct vasodilator that relaxes vascular smooth muscle, causing blood vessels to dilate and leading to a decrease in blood pressure 1. As a result, baroreceptors in the carotid sinus and aortic arch detect this change and trigger the sympathetic nervous system to increase heart rate, leading to reflex tachycardia.

Some key points to consider when using hydralazine include:

• The usual dose range for hydralazine is an initial 10 mg via slow IV infusion, with repeat doses every 4–6 h as needed 1.
• The effects of hydralazine on blood pressure begin to decrease within 10–30 min, and the fall lasts 2–4 h 1.
• Common side effects of hydralazine include headache, dizziness, flushing, palpitations, and tachycardia, but bradycardia is not typically associated with this medication.

It's worth noting that other medications, such as beta-blockers, may be prescribed alongside hydralazine to counteract the reflex increase in heart rate 1. If a patient taking hydralazine experiences bradycardia, other causes should be investigated, as this is not a typical side effect of the medication.

From the FDA Drug Label

Although the precise mechanism of action of hydrALAZINE is not fully understood, the major effects are on the cardiovascular system. HydrALAZINE apparently lowers blood pressure by exerting a peripheral vasodilating effect through a direct relaxation of vascular smooth muscle HydrALAZINE, by altering cellular calcium metabolism, interferes with the calcium movements within the vascular smooth muscle that are responsible for initiating or maintaining the contractile state The peripheral vasodilating effect of hydrALAZINE results in decreased arterial blood pressure (diastolic more than systolic); decreased peripheral vascular resistance; and an increased heart rate, stroke volume, and cardiac output.

• Hydralazine does not cause bradycardia. In fact, it results in an increased heart rate. 2

From the Research

Hydralazine and Bradycardia

• Hydralazine is generally recognized to produce hypotension accompanied by baroreflex-mediated tachycardia, but in some cases, it can cause bradycardia, a paradoxical response that has not been fully explained 3.
• A study in conscious normotensive and hypertensive rats found that hydralazine-induced hypotension was accompanied by either tachycardia, unchanged heart rate, or bradycardia, suggesting that two reflexes with opposite effects on heart rate may be initiated by hydralazine: the arterial baroreflex producing tachycardia and a cardiac mechanoreceptor reflex producing bradycardia 4.
• Another study found that hydralazine produced hypotension and tachycardia in intact rats, but hypotension and bradycardia in sino-aortic deafferented (SAD) animals, suggesting that suppression of the arterial baroreflex by SAD may propitiate the appearance of a bradycardiac response to hydralazine 3.
• However, a clinical study found that hydralazine was used to increase heart rate in patients with symptomatic sinus bradycardia, and it ameliorated symptoms and produced a 20% or greater increase in heart rate in just under two-thirds of the hypertensive and half of the normotensive patients 5.
• Other studies have reported that hydralazine may cause reflex tachycardia as an adverse effect, but its effect on clinical outcomes remains uncertain 6, 7.

Mechanism of Hydralazine-Induced Bradycardia

• The mechanism of hydralazine-induced bradycardia is not fully understood, but it may involve the activation of a vagal cardiodepressant reflex originating in the heart, as suggested by its blockade by drugs acting at various sites along the reflex arch 3.
• The cardiac mechanoreceptor reflex may also play a role in the bradycardic response to hydralazine, as it is thought to be involved in the regulation of heart rate and blood pressure 4.