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PubMed1977

Sodium nitroprusside: factors which attenuate its action. Studies with the isolated gracilis muscle of the dog.

In a laboratory preparation of the isolated, acutely denervated, and separately perfused canine gracilis muscle we have made the following observations: 1. At physiological pH, sodium nitroprusside significantly decreases the vascular resistance; 2. At physiological pH, cyanide significantly attenuates the effect of sodium nitroprusside; 3. In an acidaemic milieu, our data suggest that the effect of sodium nitroprusside may be attenuated. We speculate that patients who manifest resistance to the hypotensive effect of sodium nitroprusside may not normally eliminate the cyanide that is released from the biodegradation of sodium nitroprusside. They accumulate free cyanide which interferes with the action of sodium nitroprusside at the receptor level, leading to administration of more nitroprusside and setting in motion a positive feedback vicious cycle. When one is faced with the problem of an abnormal response to sodium nitroprusside in a fit patient, although many factors may be involved, we suggest that the possibility of rising blood cyanide levels and acidosis be given high priority.

Animals↗

PubMed1976

Effect of nitroprusside on local contractile performance after coronary ligation and reperfusion.

To study the effects of nitroprusside infusion on the regional contractile performance of the left ventricle after coronary occlusion, local tension and segment length of the ischemic, border and nonischemic zones were studied using Walton-Brodie strain gauge arches and mercury-in-Silastic tubing segment length gauges in open chest dogs. The effect of this intervention on the time period for functional reversibility of the affected areas after revascularization was also examined. Fifteen minutes after occlusion of the left anterior descending coronary artery, nitroprusside (4 to 11 mug/kg per min) was infused to keep systolic pressure 20 to 25% below control levels for 2 hours after occlusion and then 1 hour after reperfusion. The ischemic zone showed no change in either tension or length although there was a gradual continuing decrease in tension. However, in the border zone total tension which had decreased to 81.4 +/- 9.6 (standard error of the mean) percent of control level 15 minutes after coronary occlusion, increased to 87.5 +/- 11.3% immediately after nitroprusside infusion and continued at that level for 2 hours. Preejection tension rate of tension rise and ejection tension demonstrated parallel increases. Segment length, which had increased to 144.1 +/- 4.5% of control level after coronary occlusion, declined to 115 +/- 10.7% (P less than 0.02) immediately after the onset of infusion. The nonischemic zone showed a sustained increase in all tension variables (P less than 0.01) and a decrease in segment length during the period of nitroprusside infusion with a return to control value after discontinuation of the infusion. The immediate deterioration in tension in the ischemic zone caused by reperfusion after 2 hours of occlusion was prevented by nitroprusside. The border zone continued to maintain improved tension after reperfusion but exhibited an immediate decrease from 84.1 +/- 7.8% to 69.1 +/- 11.7% (P less than 0.05) after discontinuation of nitroprusside. In summary, nitroprusside infusion provides a sustained increase in tension and decrease in length of the border and the nonischemic zones after acute coronary occlusion whereas the ischemic zone remains unaffected. Although administration of nitroprusside fails to prolong the time period for functional reversibility of the affected zones with reperfusion, it appears to prevent further deterioration.

Animals↗

PubMed1990

Radial arterial pressure measurements may be a poor guide to the beneficial effects of nitroprusside on left ventricular systolic pressure in congestive heart failure.

The effect of nitroprusside on pressure wave transmission from ascending aorta to radial artery was studied in 10 patients with severe congestive heart failure. Nitroprusside resulted in a beneficial increase in cardiac index, reduction of pulmonary wedge pressure and reductions of aortic and radial arterial mean pressures. In 6 patients with an identifiable late systolic peak of aortic pressure (group I), nitroprusside reduced aortic systolic pressure more than radial systolic pressure, resulting in an increase in the difference between aortic and radial systolic arterial pressure (group I control 13 +/- 4, nitroprusside 20 +/- 6 mm Hg; p less than 0.025). Yet in 4 patients in whom no aortic late systolic pressure wave was apparent (group II), nitroprusside did not alter the difference between aortic and radial systolic pressures. Radial arterial pressure is often used to estimate the effect of nitroprusside on the arterial pressure load on the left ventricle. These results indicate that a reduction of radial systolic pressure induced by nitroprusside may underestimate the true reduction of aortic systolic pressure and thus the effect of the vasodilator on the arterial load on the left ventricle. The enhanced difference between aortic and radial arterial systolic pressures appears to be the consequence of nitroprusside on arterial pressure reflections.

Adult↗

PubMed1996

Sodium nitroprusside-induced apoptotic cellular death via production of hydrogen peroxide in murine neuroblastoma N1E-115 cells.

Sodium nitroprusside is widely used in pharmacological studies as a potent vasodilator or a nitric oxide donor. The mechanisms of cellular death induced by sodium nitroprusside were investigated in murine neuroblastoma N1E-115 cells. Sodium nitroprusside reduced the cellular viability, and the DNA extracted from treated cells showed a ladder-like intranucleosomal fragmentation pattern, which is an indication of apoptosis. The DNA fragmentations were also visualized by in situ nick translation. The cellular death was attenuated by cycloheximide, indicating that ongoing protein synthesis was essential for the initiation of the degenerative response. However, other nitric oxide donors did not decrease the cellular viability. The nitric oxide scavenger, hemoglobin, had no effect on sodium nitroprusside-induced cellular death. Furthermore, sodium cyanide, which is formed by the metabolism of sodium nitroprusside, did not cause cellular death. On the other hand, hydrogen peroxide, another product of sodium nitroprusside metabolism, reduced the cellular viability and induced DNA fragmentation. In addition, the cell damage induced by sodium nitroprusside was enhanced by a medium without fetal bovine serum. In conclusion, we proposed that hydrogen peroxide is the important toxic species for induction of apoptosis in N1E-115 cells exposed to sodium nitroprusside.

Animals↗

PubMed2006

Role of chloride transport proteins in the vasorelaxant action of nitroprusside in isolated rat aorta.

Chloride ions play a key role in smooth muscle contraction, but little is known concerning their role in smooth muscle relaxation. Here we investigated the effect of chloride transport inhibitors on the vasorelaxant responses to nitroprusside in isolated and endothelium-denuded rat aorta, precontracted with phenylephrine 1 muM. Incubation of aortic rings in NO(3)(-) media strongly potentiated the vasorelaxant responses to nitroprusside. Bumetanide, DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid) and acetazolamide strongly potentiated the vasorelaxant responses to nitroprusside (by 70-100%). EC(50) were 2.3+/-0.5 microM for bumetanide, 26+/-15 microM for DIDS and 510+/-118 microM for acetazolamide (n=6 for condition). Niflumic acid, a selective inhibitor of ClCa (calcium-activated chloride channels), potentiated nitroprusside relaxation to a similar extent as chloride transport inhibitors, in a non-additive manner. Zinc and nickel ions, both modestly potentiated nitroprusside vasorelaxation (by 20-30%). Cobaltum had negligible effect on nitroprusside vasorelaxation. CPA (p-chlorophenoxy-acetic acid), an inhibitor of volume-sensitive chloride channels (ClC), slightly potentiated nitroprusside vasorelaxation (by 15%), and the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel inhibitors CFTR(inh)172 (5-[(4-Carboxyphenyl)methylene]-2-thioxo-3-[(3-trifluoromethyl)phenyl-4-thiazolidinone), DPC (diphenylamine-2,2'-dicarboxylic acid) and glibenclamide were without significant effect. In conclusion, inhibition of chloride transport proteins strongly potentiates the vasorelaxant responses to nitroprusside in isolated rat aorta. This effect seems mediated by chloride depletion and inhibition of a chloride channel activated by both, calcium and cyclic GMP (cGMP).

Animals↗

PubMed2003

Sodium nitroprusside infusion after bidirectional superior cavopulmonary connection: preserved cerebral blood flow velocity and systemic oxygenation.

OBJECTIVE: Systemic hypertension is common in patients after bidirectional superior cavopulmonary connection. It can be treated with a vasodilator, such as sodium nitroprusside. However, it is possible that systemic hypertension is necessary to maintain cerebral blood flow in the face of cerebral venous hypertension. Furthermore, bidirectional superior cavopulmonary connection places the cerebral and pulmonary vascular beds in series. Thus treatment of systemic hypertension by lowering blood pressure might decrease cerebral blood flow, pulmonary blood flow, and systemic oxygen levels. The aim of the current study was to determine the effects of sodium nitroprusside on cerebral blood flow velocity and systemic oxygenation in patients after bidirectional superior cavopulmonary connection. METHODS: This is a prospective patient-controlled study of 9 patients (median age, 7 months; age range, 4 to 12 months) undergoing bidirectional superior cavopulmonary connection. Patients were studied in the intensive care unit within 6 hours of surgical intervention while sedated, paralyzed, and mechanically ventilated. Sodium nitroprusside was infused to achieve a decrease in mean systemic blood pressure of approximately 20%. Cerebral blood flow velocity was measured by means of transcranial Doppler ultrasonography of the middle cerebral artery. RESULTS: During sodium nitroprusside infusion, mean systemic blood pressure decreased (from 69 +/- 6 mm Hg at baseline to 58 +/- 6 mm Hg, P <.05). However, there was no accompanying change in 2 indicators of cerebral blood flow: blood flow velocity in the middle cerebral artery and arteriovenous oxygen saturation difference across the upper body. Both arterial Po(2) and systemic oxygen saturation were also preserved during sodium nitroprusside infusion. CONCLUSIONS: Sodium nitroprusside decreases systemic blood pressure in patients after bidirectional superior cavopulmonary connection. This decrease occurs without accompanying changes in cerebral blood flow velocity or systemic oxygen levels. These findings suggest that cerebral and pulmonary blood flows are preserved during sodium nitroprusside infusion. Sodium nitroprusside appears to be an appropriate agent for the treatment of systemic hypertension after bidirectional superior cavopulmonary connection.

Antihypertensive Agents↗

PubMed2000

Antiplatelet effects of sodium nitroprusside in flowing human blood: studies under normoxic and hypoxic conditions.

We explored the ability of sodium nitroprusside to modify adhesive and cohesive function of platelets in flowing blood, under normoxic and hypoxic conditions. Aliquots of both untreated and sodium nitroprusside-treated blood were prepared for studies of: (1) platelet aggregation in plasma; (2) erythrocyte deformability; (3) platelet interaction with damaged subendothelium, by using a well-defined perfusion system; and (4) blood gasometry in the perfused samples. Results showed that sodium nitroprusside-treated blood always showed a totally inhibited arachidonic acid-induced platelet aggregation in plasma, as well as significantly increased erythrocyte deformability (0.44+/-0.09 up to 0.66+/-0.05; p<0.05). However, treatment with sodium nitroprusside did not modify the pattern of platelet interaction with subendothelium (percentage of contact, adhesion, thrombus, and covered surface) with respect to untreated blood, under any of the shear rates used (300, 800, and 1800 seconds(-1)), although it significantly reduced the height of thrombi (9.8+/-0.4 vs. 8.3+/-0.4 microm; p<0.05). Hypoxic conditions did not have a noticeable effect in modifying antiplatelet effects of sodium nitroprusside. Additionally, the presence of sodium nitroprusside impaired the normal oxygenation of the blood during perfusion. pO2 in control untreated samples rose from 40.3+/-5.0 mm Hg perfusions to 100.4+/-12.5 mm Hg but remained at 66.3+/-6.3 mm Hg in sodium nitroprusside-treated blood (p<0.05). Our results did not show a significant effect of sodium nitroprusside in the modulation of platelet interaction with subendothelium. The marginal reduction in the thrombi height could be related to rheological interference of increased erythrocyte deformability.

Blood Gas Analysis↗

PubMed1985

Inotropic, vascular and neuroendocrine effects of nifedipine in heart failure: comparison with nitroprusside.

To evaluate the short-term hemodynamic and neuroendocrine effects of nifedipine in heart failure, it was compared with nitroprusside, a balanced vasodilator without known inotropic effect, in equihypotensive doses during right and left heart catheterization in nine patients with heart failure. Mean arterial pressure decreased from 89 +/- 12 to 76 +/- 14 mm Hg with nitroprusside, and from 90 +/- 12 to 75 +/- 13 mm Hg with sublingual nifedipine. Right atrial, pulmonary artery, pulmonary capillary wedge and left ventricular end-diastolic pressures decreased significantly with nitroprusside, but not with nifedipine. Cardiac index and stroke volume index increased to a similar extent with both drugs; in contrast, stroke work index increased significantly with nitroprusside, but not with nifedipine. Peak rate of left ventricular pressure development (dP/dt) (measured with a micromanometer-tipped catheter in seven patients) was unchanged with nitroprusside, but decreased significantly with nifedipine (747 +/- 292 to 639 +/- 238 mm Hg/s; p less than 0.002). There was no change in heart rate with either medication. Plasma norepinephrine and epinephrine concentrations were not altered significantly by either drug. Plasma renin activity was not changed by nitroprusside infusion, but was increased after the administration of nifedipine. Thus, in contrast to the balanced vasodilator action of nitroprusside, the effect of nifedipine is predominantly on the arterial circulation. In these patients with heart failure, reflex sympathetic stimulation did not occur in response to a decrease in systemic arterial pressure by either vasodilator. A negative inotropic effect occurred after the administration of nifedipine, but not nitroprusside.

Adult↗

PubMed1983

Effects of hydralazine and sodium nitroprusside on plasma catecholamines and heart rate.

Hydralazine and sodium nitroprusside induce different effects on systemic hemodynamics, but their effects on sympathetic neuronal activity have not been compared. Five hypertensive subjects receiving only hydrochlorothiazide were studied during two sessions. During one session, four doses of hydralazine, 0.1 to 0.6 mg/kg, were given intravenously at least 3 days apart, and during the other session, sodium nitroprusside was infused in stepwise doses, 0.05 to 4.8 micrograms/kg/min for 10 min per dose. Mean arterial pressure (MAP), heart rate (HR), and plasma norepinephrine (NE) and epinephrine concentrations were determined before and after dosing. The following correlated linearly for hydralazine and sodium nitroprusside: delta HR/delta MAP, delta NE/delta MAP, and delta HR/delta NE. Comparison of these relationships, however, indicated significant differences between the sympathetic neuronal and hemodynamic responses to hydralazine and sodium nitroprusside. Increase in HR relative to decrease in MAP was greater for hydralazine than for sodium nitroprusside. There were greater increases in plasma NE concentration relative to falls in MAP with sodium nitroprusside than with hydralazine, but increases in HR relative to increases in plasma NE concentration were smaller for sodium nitroprusside than for hydralazine. Such responses may reflect differential effects of hydralazine and sodium nitroprusside on the systemic clearance of NE or of the activity of cardiopulmonary baroreceptors.

Adult↗

PubMed1989

Nitroprusside differentially inhibits ADP-stimulated calcium influx and mobilization in human platelets.

1. The effect of nitroprusside on cGMP concn., cAMP concn., shape change, aggregation, intracellular free Ca2+ concn. (by quin-2 fluorescence) and Mn2+ entry (by quenching of quin-2) was investigated in human platelets incubated with 1 mM-Ca2+ or 1 mM-EGTA. 2. Nitroprusside (10 nM-10 microM) caused similar concentration-dependent increases in platelet cGMP concn. and was without effect on cAMP concn. in the presence of extracellular Ca2+ or EGTA. 3. In ADP (3-6 microM)-stimulated platelets, nitroprusside caused 50% inhibition of shape change at 0.4 microM (+Ca2+) or 1.3 microM (+EGTA), aggregation at 0.09 microM (+Ca2+) and of increased intracellular Ca2+ at 0.02 microM (+Ca2+) or 2.1 microM (+EGTA). Entry of 1 mM-Mn2+ (-Ca2+) was inhibited by 80% by 5 microM-nitroprusside. 4. In ionomycin (20-500 nM)-stimulated platelets, nitroprusside (10 nM-100 microM) did not inhibit shape change or intracellular-Ca2+-increase responses, and only partially inhibited aggregation. 5. In phorbol myristate acetate (10 nM)-stimulated platelets, neither shape change nor aggregation was inhibited by 5 microM-nitroprusside. 6. The data demonstrate that nitroprusside inhibits ADP-mediated Ca2+ influx more potently than Ca2+ mobilization. Nitroprusside appears not to influence Ca2+ efflux or sequestration and not to affect the sensitivity of the activation mechanism to intracellular Ca2+ concn. or activation of protein kinase C.

Adenosine Diphosphate↗

PubMed1978

Prevention of nitroprusside-induced cyanide toxicity with hydroxocobalamin.

To investigate hydroxocobalamin's role in preventing cyanide intoxication from sodium nitroprusside, we studied two groups of patients. One group received nitroprusside alone, and the other received nitroprusside and hydroxocobalamin. Red-cell and plasma cyanide levels were 83.44 +/- 23.12 and 3.51 +/- 1.01 microgram per 100 ml after nitroprusside alone and were 33.18 +/- 17.29 and 2.18 +/- 0.65 microgram per 100 ml after nitroprusside plus hydroxocobalamin. Acidosis developed in patients with red-cell cyanide levels higher than 75 microgram per 100 ml. When hydroxocobalamin infusion was stopped before sodium nitroprusside infusion was discontinued, blood cyanide levels and base deficit increased in a manner similar to that in the untreated group. The dose of nitroprusside used in each group did not differ statistically. These data show that hydroxocobalamin prevents cyanide transfer from red cells and plasma to tissue after nitroprusside metabolism, and thereby prevents cyanide toxicity from large intravenous doses of the drug.

Adult↗

PubMed1991

Hemodynamic and myocardial blood flow. Profiles of pinacidil and nitroprusside in conscious dogs.

Vasodilator antihypertensive agents can induce endocardial underperfusion relative to myocardial metabolic demand in normal hearts. We studied ten conscious normotensive dogs, paced at constant heart rate, to determine the relative probabilities of inducing endocardial ischemia with intravenous sodium nitroprusside or pinacidil, a novel antihypertensive agent. On different days, pinacidil and nitroprusside were infused in each animal to achieve mean aortic pressures (MAP) of 83 +/- 0.2 mm Hg and 62 +/- 1 mm Hg, reduced from control pressures of 106 +/- 3 mm Hg (pinacidil) and 107 +/- 3 mm Hg (nitroprusside). At MAP = 62 mm Hg, pinacidil depressed the left ventricular endocardial:epicardial blood flow (0.81 +/- 0.03) more than did nitroprusside (1.00 +/- 0.06, P less than .01). However, pinacidil increased left ventricular blood flow in all transmural layers at both levels of hypotension (P less than .05); nitroprusside increased only epicardial blood flow at MAP = 62 mm Hg (P less than .05). Neither vasodilator significantly altered myocardial oxygen consumption at either level of hypotension. At MAP = 83 mm Hg, pinacidil depressed the ratio of left ventricular vascular resistance and systemic vascular resistance indices (LVVRI/SVRI) 40 +/- 6 percent (P less than .001) to a level below that existing during nitroprusside infusion (P less than .05). These data indicate that pinacidil has greater selectivity for the coronary circulation over the systemic circulation compared to nitroprusside. Although it is unlikely that either drug caused endocardial ischemia in the present study, the data suggest that pinacidil is less likely to do so than is nitroprusside in normal hearts.

Animals↗

PubMed2000

Chemical ripening of the cervix with intracervical application of sodium nitroprusside: a randomized controlled trial.

Nitric oxide (NO) has been found to be involved in the processes of cervical ripening. In a randomized, placebo-controlled study, cervical softening by an intracervical application of sodium nitroprusside, one of the most clinically potent and effective NO donor agents, was evaluated. A total of 36 primigravid women undergoing pregnancy termination between 9 and 12.5 weeks were enrolled. In one series, 18 patients were randomized to receive intracervically either placebo or 1% nitroprusside gel (5 mg), followed by uterine evacuation 6 h after treatment. In another series, 18 patients received either placebo or 2% nitroprusside gel (10 mg) into the cervical canal followed by uterine evacuation 3 h later. The cervical resistance, i.e. the force required to dilate the cervix from 3 to 10 mm, was the main outcome variable. It was recorded using a force sensing apparatus (dynamometer). Blood pressure was measured. Adverse events were recorded until 2 h after surgery. Women treated with both doses of nitroprusside gel showed values of cervical resistance significantly lower than those treated with placebo gel, at any tested diameter. No differences were found between subjects treated with the two different doses of nitroprusside. No significant consistent changes in blood pressure were induced by either dose of nitroprusside. No headaches were found in subjects treated with the NO donor. This study demonstrates that sodium nitroprusside applied into the cervical canal induces a rapid and significant softening of the cervix, thus reducing the force required to dilate it, compared with placebo-treated subjects. The chemical ripening of the cervix with sodium nitroprusside intracervical gel is an efficacious procedure in first-trimester pregnancy.

Abortion, Induced↗

PubMed2002

In nonhuman primates intracarotid adenosine, but not sodium nitroprusside, increases cerebral blood flow.

UNLABELLED: Intracarotid infusion of short-acting vasodilators, such as adenosine and nitroprusside, in doses that lack significant systemic side effects, may permit controlled manipulation of cerebrovascular resistance. In this experiment we assessed changes in cerebral blood flow (CBF) after intracarotid infusion of nitroprusside and adenosine. The study was conducted on six adult baboons under isoflurane anesthesia and controlled ventilation. Intracarotid drug infusion protocol avoided hypotension during nitroprusside infusion and tested for autoregulatory vasoconstriction. CBF (intraarterial (133)Xe technique) was measured four times during infusions of 1) intracarotid saline, 2) IV phenylephrine (0.2 microg x kg(-1) x min(-1)) aimed to increase mean arterial pressure by 10-15 mm Hg, 3) IV phenylephrine and intracarotid nitroprusside (0.5 microg x kg(-1) x min(-1)), and 4) intracarotid adenosine (1 mg/min). IV phenylephrine increased mean arterial pressure (69 +/- 8 to 91 +/- 9 mm Hg, P < 0.0001, n = 6), and concurrent infusion of intracarotid nitroprusside reversed this effect. However, compared with baseline, CBF did not change with IV phenylephrine or with concurrent infusion of IV phenylephrine and intracarotid nitroprusside. Intracarotid adenosine profoundly increased CBF (from 29 +/- 8 to 75 +/- 32 mL x 100 g(-1) x min(-1); P < 0.0001). In nonhuman primates, intracarotid adenosine increases CBF in doses that lack significant systemic side effects, whereas intracarotid nitroprusside has no effect. Intracarotid adenosine may be useful for manipulating cerebrovascular resistance and augmenting CBF during cerebral ischemia. IMPLICATIONS: Intraarterial (133)Xe cerebral blood flow (CBF) measurements suggest that intracarotid adenosine, in a dose that lacks significant systemic side effects, profoundly increases CBF, whereas nitroprusside has no effect.(5-12)

Adenosine↗

PubMed2006

Sodium nitroprusside protects adult rat cardiac myocytes from cellular injury induced by simulated ischemia: role for a non-cGMP-dependent mechanism of nitric oxide protection.

The cardioprotective actions of nitric oxide (NO) have largely been attributed to cGMP. NO may, however, elicit some biological actions independently of cGMP. We tested the hypothesis that the NO donor sodium nitroprusside specifically protects isolated cardiomyocytes from injury at least in part independently of its ability to elevate cGMP by using metabolic inhibition to simulate ischemia. Metabolic inhibition-induced injury of adult rat cardiomyocytes (increased activity of lactate dehydrogenase and creatine kinase) was significantly reduced by sodium nitroprusside by at least 30% at all concentrations studied (0.3-100 microM). Sodium nitroprusside (1 microM) increased cardiomyocyte cGMP content, but neither a stable analogue of cGMP (8-bromo-cGMP) nor a potent cGMP stimulus (atrial natriuretic peptide) mimicked the protective effects of sodium nitroprusside. Moreover, inhibition of soluble guanylyl cyclase failed to inhibit sodium nitroprusside cardiomyocyte protection. Conversely, inhibition of either ATP-sensitive potassium (K(ATP)) channels with glibenclamide (10 microM) or calcium-sensitive potassium (K(Ca)) channels with tetraethylammonium bromide (1 mM) or iberiotoxin (20 nM) markedly attenuated the cardioprotective actions of sodium nitroprusside. In conclusion, sodium nitroprusside protects isolated cardiomyocytes from metabolic inhibition independently of cGMP; rather, inhibition of K(Ca) and K(ATP) channels reverses the sodium nitroprusside actions, thus unmasking another mechanism for NO-mediated protection in cardiomyocytes.

Animals↗

PubMed1981

A comparative study of the relaxing effect of nitroprusside and verapamil on human umbilical vessels.

Relaxing effects of nitroprusside and verapamil on the resting or K-stimulated tension and 45Ca uptake in human umbilical vessels were investigated. Both nitroprusside and verapamil reduced the resting and K-stimulated tensions in a dose-dependent manner. Nitroprusside was much more effective than verapamil in reducing resting tension. However, verapamil caused a greater relaxation of the K-induced contraction than nitroprusside. In a Ca2+-free medium, K+ still caused a small and sustained contraction. Nitroprusside abolished the contraction in the Ca2+-free medium, which verapamil failed to inhibit. Neither nitroprusside nor verapamil affected the resting 45Ca uptake measured by a lanthanum method. The K-induced increase in 45Ca uptake was inhibited by verapamil, but not by nitroprusside. The results suggest that nitroprusside unlike verapamil does not act as a Ca2+ influx inhibitor resulting in the relaxation of human umbilical vessels.

Calcium↗

PubMed1982

Comparison of intravenous nitroglycerin and sodium nitroprusside for treatment of acute hypertension developing after coronary artery bypass surgery.

The present study was designed to test the hypothesis that i.v. nitroglycerin is as effective as sodium nitroprusside for managing acute hypertension early after coronary artery bypass surgery. Seventeen patients received both nitroglycerin and nitroprusside in a randomized crossover protocol. Infusion rates were increased stepwise to lower mean arterial pressures comparably with each drug. In 14 of 17 patients, similar infusion rates of the two vasodilators resulted in equal lowering of both blood pressure and systemic vascular resistance. In the remaining three patients, very high infusion rates of nitroglycerin were required and achieved only 20-50% of nitroprusside's response in two of three. Hemodynamic responses to the two vasodilators were similar, except that nitroglycerin increased cardiac output more than nitroprusside did. In contrast, pulmonary gas exchange responses differed in that nitroglycerin improved intrapulmonary shunting, while nitroprusside worsened it. Similarly, nitroglycerin resulted in a significantly smaller increase in the alveolar arterial oxygen gradient than did nitroprusside. These results suggest that in the majority of patients, i.v. nitroglycerin was as effective as nitroprusside in controlling acute hypertension after coronary artery bypass surgery. In addition, nitroglycerin appeared to have more favorable effects on pulmonary gas exchange. Because nitroglycerin has more beneficial effects on intercoronary collateral blood flow in the setting of regional ischemia, it may be preferable to nitroprusside in patients with ischemic heart disease.

Blood Pressure↗

PubMedDate not supplied

Clinical pharmacokinetics of nitroprusside, cyanide, thiosulphate and thiocyanate.

Sodium nitroprusside decomposes within a few minutes after intravenous infusion to form metabolites which are pharmacologically inactive but toxicologically important. Free cyanide, which represents 44% w/w of the sodium nitroprusside molar mass, is formed and must be detoxified in the body into thiocyanate using thisulphate as substrate. Nitroprusside penetrates cell membranes slowly. At therapeutic dose levels its distribution is probably mainly extracellular. Contact with the sulfhydryl groups in the cell walls, however, immediately initiates breakdown of the molecule. Sodium nitroprusside taken orally is not absorbed from the gastrointestinal tract to any appreciable extent. Cyanides in the body form prussic acid, which can rapidly penetrate mucous and cell membranes. In the blood, about 99% of the prussic acid binds to the methaemoglobin of erythrocytes. At normal physiological levels, however, the total body methaemoglobin of an adult human can only bind about 10mg of prussic acid; this is a small fraction of the amounts usually infused therapeutically as sodium nitroprusside. The endogenous detoxification of prussic acid exhibits zero-order kinetics. The limiting factor is a sulphur donor, principally thiosulphate, which is available in the body in only limited amounts. The rate of spontaneous detoxification of prussic acid in humans is only about 1 microgram/kg/min, corresponding to a sodium nitroprusside infusion of about 2 microgram/kg/min. This dose limit set by the prussic acid toxicity of sodium nitroprusside can, however, be increased considerably by simultaneous infusion of thiosulphate. A lack of thiosulphate can be detected early by a rise of the prussic acid concentration in the erythrocytes. Thiosulphate taken orally is not absorbed by the body. After intravenous infusion, its serum half-life is about 15 minutes. Most of the thiosulphate is oxidised to sulphate or is incorporated into endogenous sulphur compounds; a small proportion is excreted through the kidneys. Thiocyanate taken orally is completely absorbed by the body. In healthy persons its volume of distribution is approximately 0.25 L/kg and the serum half-life about 3 days; elimination is mainly renal. Thiocyanate toxicity does not represent a serious therapeutic problem with intravenous infusion of sodium nitroprusside.

Biotransformation↗