Mechanism
of action
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. It has also been suggested that cyclic 3',5'-adenosine monophosphate
(cyclic AMP) mediates, at least partly, the relaxation of arterial smooth
muscle by altering cellular calcium metabolism, which interferes with the
calcium movements within the vascular smooth muscle that are responsible for
initiating or maintaining the contractile state. In hypertensive patients, the
hydralazine-induced decrease in blood pressure is accompanied by increased
heart rate, cardiac output, and stroke volume, probably because of a reflex
response to decreased peripheral resistance. The drug has no direct effect on
the heart. Hydralazine may increase pulmonary arterial pressure, as well as
coronary, splanchnic, cerebral, and renal blood flow. The preferential
dilatation of arterioles, as compared to veins, minimizes postural hypotension
and promotes the increase in cardiac output. Hydralazine usually increases
renin activity in plasma, presumably as a result of increased secretion of
renin by the renal juxtaglomerular cells in response to reflex sympathetic
discharge. This increase in renin activity leads to the production of
angiotensin II, which then causes stimulation of aldosterone and consequent
sodium reabsorption. Tolerance to the antihypertensive effect of the drug
develops during prolonged therapy, especially if a diuretic is not administered
concurrently. In patients with CHF, hydralazine decreases systemic vascular
resistance and increases cardiac output.
Reference: Tripathi K.D., “Essentials of
Medical Pharmacology”, Jaypee brothers medical publishers, Seventh edition, New
Delhi, page no. 520,522,559.
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