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Nitrite Pharmacodynamics and the Hemodynamics of Angina

JAMA. 1973;223(7):796. doi:10.1001/jama.1973.03220070050014.
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When little over a century ago nitrites were introduced into clinical medicine, their mechanism of action was not in doubt. Known to be potent smooth muscle relaxants, they were supposed to relieve angina by relaxing "spastic" coronary arteries. As coronary "spasm" became an obsolete concept, they were assumed to exercise their muscle relaxing action in dilating narrowed coronary vessels, thereby augmenting the blood supply to the ischemic myocardium. Investigations centered on the effect of these drugs on coronary blood flow.

These traditional views have been disputed by Gorlin et al1 and other investigators. Having observed that anginal pain could be alleviated by nitrites without demonstrable change in coronary blood flow, they looked for an explanation of nitrite effects not in the coronary but in the peripheral circulation as it relates to the mechanism of anginal pain. And viewing angina as a discrepancy between coronary blood flow and myocardial oxygen demand,

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