What is the mechanism of action of hydralazine?

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.

How does hydralazine affect vasculature?

Hydralazine, which is highly specific for arterial vessels, reduces systemic vascular resistance and arterial pressure. Indirect cardiac stimulation (e.g., tachycardia) occurs with hydralazine administration because of activation of the baroreceptor reflex.

How do hydralazine and nitrates affect vasculature?

Pharmacologic action With proper dose selection, the hydralazine-nitrate combination provides balanced afterload-preload reduction with a lowering of ventricular filling pressure, and systemic and pulmonic vascular resistance.

What causes vascular smooth muscle contraction?

Vascular smooth muscle cells are highly plastic and in pathological conditions undergo phenotypic changes from a contractile to a proliferative state. Vascular smooth muscle contraction is triggered by an increase in intracellular free calcium concentration ([Ca2+]i), promoting actin–myosin cross-bridge formation.

Which is a novel mechanism of action for hydralazine?

represent a novel mechanism of action. Hydralazine induced rapid and transient expression of HIF-1 and downstream targets of HIF (endothelin-1, adrenomedullin, haem oxygenase 1, and vascular endothelial growth factor [VEGF]) in endothelial and smooth muscle cells and induced endothelial cell-specific proliferation. Hydralazine dose-dependently

How is hydralazine converted to active pyruvic acid?

Hydralazine is spontaneously converted to the active pyruvic acid hydrazone or the pyruvic acid hydrazone tricyclic dehydration product, and these metabolites can convert back and forth between these 2 forms. 1, 5 Hydralazine can be converted to hydrazinophthalazinone, which is further converted to the active acetylhydrazinophthalazinone. 1, 4

What is the bioavailability of hydralazine with food?

Taking oral hydralazine with food improves the bioavailability of the drug. 13 An intravenous dose of 0.3mg/kg leads to an AUC of 17.5-29.4µM*min and a 1mg/kg oral dose leads to an AUC of 4.0-30.4µM*min. 14 The C max of oral hydralazine is 0.12-1.31µM depending on the acetylator status of patients. 14

What are the mechanisms of vascular smooth muscle contraction?

We review here the current understanding of the molecular mechanisms by which agonists, therapeutics, and diseases regulate contractility of the vascular smooth muscle cell and we place this within the context of whole body function.