HYDRALAZINE AND
NITRATES
A major advance in the
pharmacological management of CHF has been the demonstration that afterload
re-duction improved survival. The concept of afterload reduction was developed
for the treatment of mitral re-gurgitation. It was noted that a decrease in
systemic vas-cular resistance, as reflected in lower arterial blood pres-sure,
resulted in an increase in the percentage of blood that flowed from the left
ventricle to the aorta as op-posed to the left atrium (decreased regurgitant
fraction). The decrease in backup of blood into the lungs provided considerable
symptomatic relief from dyspnea, fatigue, and chest pain. It was reasoned that
patients with CHF often also have mitral regurgitation and might similarly
benefit from more forward (left ventricle to aorta), as opposed to backward
(left ventricle to left atrium), blood flow. A VA Cooperative Study in which vasodila-tors
were added to digitalis and furosemide was the first to demonstrate a
significant improvement in survival in CHF. Patients were given either prazosin
as an α- adrenoceptor blocking agent or the combination of the direct
vasodilator hydralazine and a nitric oxide– mediated vasodilator, that is, one
of the nitrates. There were fewer deaths among the patients on the combina-tion
of hydralazine and nitrates. Patients taking prazosin did not benefit, probably
because chronic therapy with prazosin results in tachyphylaxis. The mechanisms
of ac-tion of prazosin, hydralazine, and organic nitrates are discussed in more
detail elsewhere.
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