Nitrates nitric oxide released from

In this metho d [ 124 ] nitrate, nitrate plus nitrite or nitrite alone are selectively reduced to nitric oxide, which is swept from the sample in a helium carrier gas flow. Nitric oxide is allowed to react with ozone in a nitrogen oxide analyser, where it forms nitrogen dioxide. The return of the nitrogen dioxide to the ground state is accompanied by release of a photon, which is detected by a photomultiplier. The integrated output of the photomultiplier over the time that the nitric oxide is pinged from the sample is proportional to the nitrite content of the sample. 

Fig. 1. The EDRF/NO pathway in vascular smooth muscle. Vasodilatation by nitrates at a cellular level. Nitrates, nitrites, and nitroprusside-Na are able to release nitric oxide (NO), which stimulates the conversion of GTP into cyclic guanosine monophosphate (cGMP), thus causing vasodilatation. The release of EDRF (=NO) from endothelial cells can be stimulated by various endogenous compounds. Endogenous EDRF (=NO) then causes vasodilatation, similar to the NO released by...

Release of nitric oxide from drug or endothelium Nitroprusside, hydralazine, nitrates,1 histamine, acetylcholine... 

As described below, tolerance is an important consideration in the use of nitrates. While tolerance may be caused in part by a decrease in tissue sulfhydryl groups, it can be only partially prevented or reversed with a sulfhydryl-regenerating agent. The site of this cellular tolerance may be in the unknown reaction responsible for the release of nitric oxide from the nitrate, since other agents, eg, acetylcholine, that cause vasodilation via release of nitric oxide from endogenous substrates do not show cross tolerance with the nitrates. 

It has been suggested that the lesser potency of the nitrates in dilating arterioles is the result of a reduced ability of these vessels to release nitric oxide from the parent nitrate molecule. 

The nitrates act by releasing nitric oxide, which relaxes vascular smooth muscle. The discovery that endothelium-derived relaxing factor (EDRF) is nitric oxide (1) stimulated new interest in these drugs, as nitric oxide not only controls local vessel wall tension in response to shear stress, but also plays a role in regulating the interaction of platelets with blood vessel walls. The release of nitric oxide from the walls of atheromatous arteries is reduced, because of malfunctioning or absent endothelium. Atheromatous arteries behave differently from healthy arteries, in that these vessels vasoconstrict rather than vasodilate when stimulated by acetylcholine. This impairment of the acetylcholine vasomotor response appears to be related to serum cholesterol concentration (2). 

One SL nitroglycerin (NTG) tablet should be administered every 5 minutes for up to three doses to relieve myocardial ischemia. If patients have previously been prescribed sublingual NTG and ischemic chest discomfort persists for more than 5 minutes after the first dose, the patient should be instructed to contact emergency medical services before self-administering subsequent doses in order to activate emergency care sooner. IV NTG then should be initiated in all patients with an ACS who do not have a contraindication and who have persistent ischemic symptoms, heart failure, or uncontrolled blood pressure, and should be continued for approximately 24 hours after ischemia is relieved (see Table 16-4). Importantly, other life-saving therapy, such as ACE inhibitors or /3-blockers, should not be witheld because the mortality benefit of nitrates is unproven. Nitrates promote the release of nitric oxide from the endothelium, which results in venous... 

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