Sodium Nitroprusside SNP

The nitrovasodilator sodium nitroprusside (SNP) has been used for decades to manage acute hypertensive crises and congestive heart failure complicating myocardial ischemia [99]. However, prolonged SNP administration is limited by tolerance, the 

A meta-analysis of the collective outcome results from three randomized, controlled intravenous SNP trials suggested that intravenous SNP reduces early mortality by =35% in acute myocardial infarction [78]. Since each of the component trials was 

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As well as NONOates, other NO donors also showed anticancer activity independently. Sodium nitroprusside (SNP), a metal-NO complex, showed cytotoxic effects on the cells of some patients with malignant lymphoma (ML), acute myelocytic leukemia (AML) or chronic myelomonocytic leukemia (CMMoL), but not with multiple myeloma [109]. SNP and cytosine arabinoside (Ara-C) did not share the drug resistance. Interestingly, SNP had no effect on lymphocytes of healthy volunteers. These results suggest that SNP has an anti-tumor effect on human hematological malignant cells. 

Sodium nitroprusside (SNP), which is also known as Nipruss or Nipride to medical practitioners, was the first iron nitrosyl complex, prepared as far back as 1850 by Playfair [40]. The hypotensive property of SNP was first demonstrated by Johnson [41] in 1929. It was shown that application of a moderate dose of SNP reduces the blood pressure of a severely hypertensive patient without any side effect [42]. Since that time considerable research has been carried out to understand the mode of action of nitroprusside and its metabolic fate. SNP is now regarded as a potent vasodilator that causes muscle relaxation by releasing NO which activates the cytosolic isozyme of guanylyl cyclase [43-46]. 

Although its mode is uncertain, sodium nitroprusside (SNP) is one of the most valuable vasodilators. Its use in clinical practice is suspect as the cyano-ligands render cyanide poisoning a possibility. However for ex vivo experiments this consideration is less important but the possibility of some biological action due to these ions remains. The mechanism by which SNP acts as a vasodilator is not fully understood. With the discovery of a physiological role for NO there has been renewed interest in mechanistic studies of reactions involving SNP and a re-examination of studies of SNP undertaken before 1987. So far, only one simple reaction leading to the release... 

Sodium nitroprusside (SNP) is both a venous and an arterial vasodilator. An important part of its vasodilator action is caused by the release of nitric oxide (NO), similarly as for the organic nitrates. SNP can only be administered via the intravenous route. It is a rapidly and short acting vasodilator. It has been used in the treatment of hypertensive emergencies and in the management of myocardial ischaemia. In spite of its vasodilator action it hardly influences heart rate, in contrast to hydralazine and minoxidil. The dosage of SNP should not be higher than 3 pg/kg/min within 48 h, in order to avoid the rise of cyanide ions and thiocyanate in the blood. 

Exposure of rat primary mixed hippocampal cell cultures to either sodium nitroprusside (SNP 100 xM) or 3-morpholinosydnonimine resulted in both a decrease in cell survival and an increase in free-radical accumulation. These SNP-induced events were blocked by either EGb 761 (10 to 100 pg/ml) or its flavonoid fraction CP 205 (25 pg/ml), as well as by inhibitors of protein kinase C (PKC chelerythrine) and 1-type calcium channels (nitrendipine). In contrast, the terpenoid constituents of EGb 761, known as bilobalide and ginkgolide B, as well as inhibitors of phospholipases A [3-[4-octadecyl)benzoyl]acrylic acid (OBAA)] and C (U-73122), failed to display any significant effects. Moreover, EGb 761 (50 pg/ml), CP 205 (25 pg/ml), and chelerythrine were also able to rescue hippocampal cells preexposed to SNP (up to 1 mM). Finally, EGb 761 (100 g/ml) was shown to block the activation of PKC induced by SNP (100 xM). These data suggest that the protective and rescuing abilities of EGb 761 are not only attributable to the antioxidant properties of its flavonoid constituents but also by their ability to inhibit NO-stimulated PKC activity (Figure 36.1). 

For L = CN , the low-spin Fe(III) complex leads to sodium nitroprusside (SNP) as an irreversibly formed product. The proposed mechanism implies a slow associative, reductive step by NO, followed by the fast coordination of NO+ to the [Fen(CN)5H20]3 intermediate.17 Faster reversible reactions are onset with high-spin Fe(III) porphyrins, as shown in Section 7.3.2.5... 

Sodium nitroprusside (SNP), hydrocortisone 21-hemisuccinate, desipra-mine hydrochloride, L-arginine hydrochloride, and w-conotoxin GVIA were purchased from Sigma Chemical Company (St. Louis, MO). Acid-washed alumina, sodium octyl sulfate, and catecholamine standards were purchased... 

FIGURE 2 Effects of sodium nitroprusside (SNP 1 /xM) and N -niethyl-L-arginine (NMA 300 /xM), alone or in the presence of an L-arginine (Arg) excess (1.2 raM), on the vasoconstriction (A) and norepinephrine (NE) release (B) evoked by adrenergic nerve stimulation (30 sec at 4 Hz) in the mesenteric arterial bed of the rat perfused with the o 2-adrenoeeptor antagonist yohimbine (1 /aAl). Values are expressed as the means of six experiments.. Significantly different from control values by the Newman-Keuls test at P < 0.05. For other details see the legend to Fig. 1. 

When the effect of nitric oxide donors on cGMP-accumulation is studied, one must take into account the rate of NO-release from the donor compound The diffusion rate of NO is quite high, because of the small size and hpophihcity of this molecule (45), Sodium nitroprusside (SNP) is often used an NO-donor. This compound is inexpensive, which is an important asset. However, the byproduct after NO-release, [Fe(CN)5], is not devoid of pharmacological activity (46) In addition, SNP is light sensitive, although in most cases this property should not rule out use of this compound. In 10-min incubations with brain slices, SNP and the NO-donors S-nitroso-acetyl-penicillamine and streptozotocin were equally effective in raising cGMP levels (unpublished). 

The rate constants for production of the RNS described in Table 1 vary from the order of 10 (mol/L) s to the diffusion limiting rate, which suggests an indirect and sometimes undesirable action of NO, in biological medium. Some known NO-donor agents such as glyceryl trinitrate, pen-taerythrityl tetranitrate, isosorbide mononitrate, and sodium nitroprusside (SNP) have current application in clinical therapy. Diazeniumdiolates,... 

Endogenous NO appears to play an inhibitory role in CB O2 sensing. Our laboratory reported that a NOS inhibitor (L-NAME) augmented hypoxie responses in perfused cat CBs (10). Enhanced hypoxie responses were reversed with L-arginine, the required precursor for NO production. Furthermore, inereased chemosensory excitation after L-NAME eould be eliminated by the NO donor sodium nitroprusside (SNP). Also, other investigators have reported that the CB response to hypoxia is inhibited after adding NO gas to the perfusate (11). 

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