Abstract
The mechanism of nitroglycerin-induced vasodilation was examined in isolated arteries. Nitroglycerin relaxed the large coronary artery preferentially whereas nitroprusside and the so-called non-specific vasodilators showed the same activities on both the large and small coronary arteries. Nitroglycerin-induced vasodilation but not the vasodilation induced by the other agents was antagonized markedly by pretreatment with CuSO 4. Other metal ions except Fe 2+ had no antagonizing effect. The Cu 2+-induced antagonism was restored by treatment with sulfhydryl reagents. Nitroglycerin formed inorganic nitrite by non-enzymatic reaction with the tissue sulfhydryl groups; the reaction was also inhibited by Cu 2+. Cu 2+ suppressed the membrane stabilizing effect of Ca 2+. It seems that nitroglycerin reacts with the sulfhydryl groups on the inner surface of the cell membrane, which may take part in the selectivity of this drug, and subsequently the intermediate(s) formed may activate guanylate cyclase.
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