Does hydralazine (direct vasodilator) affect heart rate?

From the Guidelines

Hydralazine does affect heart rate, typically causing an increase in heart rate (tachycardia) due to its vasodilatory effects and subsequent activation of compensatory mechanisms. This reflex tachycardia is a result of hydralazine's primary action of dilating arterioles, reducing peripheral vascular resistance, and lowering blood pressure 1. In response to this blood pressure drop, the body activates the sympathetic nervous system and the renin-angiotensin-aldosterone system, which increase heart rate and cardiac output to maintain adequate tissue perfusion.

The use of hydralazine is often considered in the context of resistant hypertension, where it is recommended to be used in combination with other agents, such as nitrates, and with careful consideration of the patient's volume status and potential need for diuretic therapy 1. The choice of a fifth drug, such as hydralazine, depends on sympathetic drive as assessed in part by heart rate, and agents like β-blockers or central α−2 agonists may be considered to counteract the reflex tachycardia caused by hydralazine 1.

Key points to consider when using hydralazine include:

• Total daily doses should be <150 mg to avoid drug-induced systemic lupus erythematosus 1
• Hydralazine should be used in the presence of background appropriate diuretic and β-blocker therapy to mitigate its effects on heart rate and volume status 1
• The addition of hydralazine/isosorbide dinitrate may be considered in certain patient populations, such as black patients with NYHA class III or IV heart failure 1

Overall, the increase in heart rate associated with hydralazine therapy is a significant consideration in its use, and careful management with concomitant medications and monitoring of patient response is necessary to optimize outcomes.

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 affects heart rate by increasing it, as a result of its peripheral vasodilating effect, which leads to decreased peripheral vascular resistance and subsequent reflex sympathetic discharge.
• The increase in heart rate is accompanied by increases in stroke volume and cardiac output. 2

From the Research

Effects of Hydralazine on Heart Rate

• Hydralazine, a direct vasodilator, can affect heart rate in various ways, as evidenced by several studies 3, 4, 5, 6, 7.
• According to a study published in 1987, hydralazine and its derivatives can evoke reflex tachycardia in response to lowering of blood pressure in normotensive or hypertensive subjects 3.
• However, another study published in 2003 found that hydralazine can induce bradycardia in sino-aortic deafferented conscious rats, suggesting that the accompanying heart rate change can be paradoxical and dependent on the experimental conditions 4.
• A review of hydralazine's effects on essential hypertension, published in 2011, noted that one of the adverse effects related to hydralazine is reflex tachycardia 5.
• A study comparing the effects of nifedipine versus hydralazine on sympathetic activity and cardiac function in patients with hypertension found that hydralazine increased plasma norepinephrine, which can lead to increased heart rate 6.
• Another review published in 2010 also mentioned reflex tachycardia as one of the adverse effects of hydralazine, but noted that the effect of hydralazine on clinical outcomes remains uncertain 7.

Key Findings

• Hydralazine can cause reflex tachycardia in response to lowering of blood pressure 3, 5, 7.
• The effect of hydralazine on heart rate can be paradoxical and dependent on the experimental conditions 4.
• Hydralazine can increase plasma norepinephrine, leading to increased heart rate 6.
• The clinical outcomes of hydralazine treatment remain uncertain, and more research is needed to fully understand its effects on heart rate and other cardiovascular parameters 5, 7.