2.Other smooth muscle organs Relaxation of smooth muscle of the bronchi, gastrointestinal tract (including biliary system),and genitourinary tract has been demonstrated experimentally.Because of their brief duration,these actions of the nitrates are rarely of any clinical value.During recent years,the use of amyl nitrite and isobutyl nitrite by inhalation as purported recreational(sex-enhancing)drugs has become popular with some segments of the population.Nitrites release nitric oxide in erectile tissue as well as vascular smooth muscle and activate guanylyl cyclase.The resulting increase in cGMP causes dephosphorylation of myosin light chains and relaxation(Figure 2),which enhances erection. 3.Action on platelets Nitric oxide released from nitroglycerin stimulates guanylyl cyclase in platelets as in smooth muscle.The increase in cGMP that results is responsible for a decrease in platelet aggregation.Unfortunately,recent prospective trials have established no survival benefit when nitroglycerin is used in acute myocardial infarction. 4.Other effects Nitrite ion reacts with hemoglobin(which contains ferrous iron)to produce methemoglobin (which contains ferric iron).Because methemoglobin has a very low affinity for oxygen,large doses of nitrites can result in pseudocyanosis, tissue hypoxia,and death.Fortunately,the plasma level of nitrite resulting from even large doses of organic and inorganic nitrates is too low to cause significant methemoglobinemia in adults.However,sodium nitrite is used as a curing agent for meats.In nursing infants,the intestinal flora is capable of converting significant amounts of inorganic nitrate,eg,from well water,to nitrite ion.Thus,inadvertent exposure to large amounts of nitrite ion can occur and may produce serious toxicity. One therapeutic application of this otherwise toxic effect of nitrite has been discovered.Cyanide poisoning results from complexing of cytochrome iron by the CN ion.Methemoglobin iron has a very high affinity for CN;thus,administration of sodium nitrite (NaNO2)soon after cyanide exposure will regenerate active cytochrome.The cyanmethemoglobin produced can be further detoxified by the intravenous administration of sodium thiosulfate (Na2S2O3);this results in formation of thiocyanate ion (SCN),a less toxic ion that is readily excreted. Methemoglobinemia,if excessive,can be treated by giving methylene blue intravenously. DRUGS USED IN THE TREATMENT OF ERECTILE DYSFUNCTION Erectile dysfunction in men has long been the subject of research(by both amateur and professional scientists).Among the substances used in the past and generally discredited are "Spanish Fly"(a bladder and urethral irritant),yohimbine,nutmeg,and 88 2. Other smooth muscle organs Relaxation of smooth muscle of the bronchi, gastrointestinal tract (including biliary system), and genitourinary tract has been demonstrated experimentally. Because of their brief duration, these actions of the nitrates are rarely of any clinical value. During recent years, the use of amyl nitrite and isobutyl nitrite by inhalation as purported recreational (sex-enhancing) drugs has become popular with some segments of the population. Nitrites release nitric oxide in erectile tissue as well as vascular smooth muscle and activate guanylyl cyclase. The resulting increase in cGMP causes dephosphorylation of myosin light chains and relaxation (Figure 2), which enhances erection. 3. Action on platelets Nitric oxide released from nitroglycerin stimulates guanylyl cyclase in platelets as in smooth muscle. The increase in cGMP that results is responsible for a decrease in platelet aggregation. Unfortunately, recent prospective trials have established no survival benefit when nitroglycerin is used in acute myocardial infarction. 4. Other effects Nitrite ion reacts with hemoglobin (which contains ferrous iron) to produce methemoglobin (which contains ferric iron). Because methemoglobin has a very low affinity for oxygen, large doses of nitrites can result in pseudocyanosis, tissue hypoxia, and death. Fortunately, the plasma level of nitrite resulting from even large doses of organic and inorganic nitrates is too low to cause significant methemoglobinemia in adults. However, sodium nitrite is used as a curing agent for meats. In nursing infants, the intestinal flora is capable of converting significant amounts of inorganic nitrate, eg, from well water, to nitrite ion. Thus, inadvertent exposure to large amounts of nitrite ion can occur and may produce serious toxicity. One therapeutic application of this otherwise toxic effect of nitrite has been discovered. Cyanide poisoning results from complexing of cytochrome iron by the CN- ion. Methemoglobin iron has a very high affinity for CN- ; thus, administration of sodium nitrite (NaNO2) soon after cyanide exposure will regenerate active cytochrome. The cyanmethemoglobin produced can be further detoxified by the intravenous administration of sodium thiosulfate (Na2S2O3); this results in formation of thiocyanate ion (SCN- ), a less toxic ion that is readily excreted. Methemoglobinemia, if excessive, can be treated by giving methylene blue intravenously. DRUGS USED IN THE TREATMENT OF ERECTILE DYSFUNCTION Erectile dysfunction in men has long been the subject of research (by both amateur and professional scientists). Among the substances used in the past and generally discredited are "Spanish Fly" (a bladder and urethral irritant), yohimbine, nutmeg, and