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PubMed1990

Metabolic effects of sodium nitroprusside on the pig kidney in vivo: studies by phosphorus-31 magnetic resonance spectroscopy.

Phosphorus-31 magnetic resonance spectroscopy was applied to the pig kidney in vivo to determine the metabolic effects of infusion of sodium nitroprusside, and of more severe hypotension produced by venesection or halothane. Sodium nitroprusside 7-20 micrograms kg-1 min-1 reduced mean systemic arterial pressure (AP) of the pig from 89 to 46 mm Hg. Glomerular filtration rate and total sodium reabsorption were reduced proportionally. Renal metabolism, assessed by the ratio [ATP]: [Pi] (inorganic phosphate), did not change. Adding halothane or venesection to nitroprusside hypotension caused a further reduction in systemic AP to 42 and 39 mm Hg, respectively. Renal [ATP] decreased in direct proportion to mean AP. It is concluded that sodium nitroprusside, even in high doses, does not reduce renal oxygen delivery as assessed by the ability of the kidney to maintain normal ATP content. However, haemorrhage or an increase in halothane dosage results in irreversible damage to the energy producing processes of the kidney. This may be relevant to the clinical use of the drug.

Adenosine Triphosphate↗
PubMed1982

Paradoxical bradycardia following the administration of sodium nitroprusside in the rat is abolished by indomethacin.

Severe bradycardia and hypotension associated with the administration of organic nitrates or nitrites has been observed in patients with ischaemic heart disease and hypertension. Experiments were performed on rats to elucidate the mechanism by which these vasodilators may effect their anomalous bradycardia-hypotensive effect. In sodium pentobarbital (50 mg.kg-1, ip) anaesthetised rats of the Wistar strain, hypotension and a paradoxical bradycardia were observed following the intra-arterial injection of 10 microgram.kg-1 sodium nitroprusside or 1 mg.kg-1 arachidonic acid. Bilateral vagotomy abolished the bradycardia to both sodium nitroprusside and arachidonic acid but did not eliminate their hypotensive effects. Indomethacin (5 mg.kg-1) abolished the blood pressure and heart rate responses to arachidonic acid. However, indomethacin abolished only the bradycardia to sodium nitroprusside without reducing its effect on blood pressure. These data suggest that in the rat sodium nitroprusside can stimulate prostaglandin biosynthesis which then initiates a reflex bradycardia.

Animals↗
PubMed2003

Effects of L-arginine and sodium nitroprusside on the spontaneous contractility of human non-pregnant uterus.

BACKGROUND: The aim of this study was to investigate, in isolated human non-gravid myometrium, the involvement of the cyclic guanosine monophosphate (cGMP) pathway in nitric oxide (NO) induced relaxation. METHODS: Strips of human myometrium from hysterectomized women were suspended in organ baths for recording of isometric tension. Cumulative concentration-response curves for L-arginine and sodium nitroprusside were performed in the presence of methylene blue (10 micromol/l) or vehicle (control). The effect of increasing concentrations of 8-bromo-cGMP on uterine spontaneous contraction was also studied. RESULTS: L-arginine and sodium nitroprusside induced a concentration-dependent decrease in the amplitude of the myometrial spontaneous contractions. Pre-treatment with methylene blue enhanced the inhibitory effect of L-arginine and sodium nitroprusside on myometrial spontaneous contractions. In addition, 8-bromo-cGMP had no effect on spontaneous contractions in human myometrium. CONCLUSIONS: These data provide evidence that L-arginine and sodium nitroprusside inhibit the spontaneous contractions of the non-pregnant human uterus through a cGMP independent pathway.

Arginine↗
PubMed2006

Mutagenesis induced by the nitric oxide donor sodium nitroprusside in mouse cells.

Nitric oxide (NO) is an important bioactive molecule derived from endogenous or exogenous sources. NO can exhibit genotoxicity through the formation of reactive nitrogen species. Nitric oxide releasing compounds, such as sodium nitroprusside, are widely used for the therapy of hypertension and other disorders. Here we have characterized the mutagenicity of sodium nitroprusside in mouse embryo fibroblasts carrying the cII mutation reporter gene. Sodium nitroprusside dose-dependently increased the cII mutant frequency to levels approximately 5-fold above background. The mutational spectrum induced by sodium nitroprusside was characterized by an increase in the fraction of G-->T transversion mutations (P < 0.003) but the proportion of transition mutations was not increased. We discuss the potential origin of the G-->T mutations induced by this compound in mammalian cells.

Animals↗
PubMed1991

Piroximone, dobutamine and nitroprusside: comparative effects on haemodynamics in patients with congestive heart failure.

Four intravenous doses of piroximone, an imidazolone derivative, were administered to 12 patients with congestive heart failure to produce a four-point dose-response curve. The haemodynamic effects were compared with those of dobutamine and nitroprusside, the substances being given sequentially and in randomized order. Piroximone and dobutamine significantly and similarly increased cardiac index (CI) and stroke volume index (SVI). Nitroprusside produced no such effect. By contrast, piroximone and nitroprusside significantly and similarly decreased mean pulmonary artery pressure (MPAP), pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP) and pulmonary vascular resistance (PVR), while such changes were not seen following dobutamine. Direct comparisons between the agents were made at doses that lowered systemic vascular resistance (SVR) to the same extent. The major difference between dobutamine and piroximone was an apparent additional vasodilator activity displayed by piroximone as demonstrated by a significantly greater decrease in MPAP, PCWP and RAP for a matched reduction in SVR and a similar increase in CI. The major difference between nitroprusside and piroximone was the significantly higher increase in CI and SVI elicited by piroximone for a matched reduction in SVR and a similar decrease in PCWP and RAP. The changes in loading conditions being equivalent, the higher increase in CI is likely to be accounted for by a direct inotropic activity.

Adult↗
PubMed1995

Beta 2-adrenoceptor density of human lymphocytes after nitroprusside-induced hypotension.

The present study was undertaken to assess the influence of nitroprusside-induced hypotension on beta 2-adrenoceptor density. Twenty-four patients undergoing nose-septum corrections under general anesthesia were allocated randomly to a nitroprusside or control group. beta 2-Receptor density on lymphocytes was measured by binding studies using (-)125-iodocyanopindolol. Lymphocyte subpopulations B, T, Thelper, Tsuppressor, and natural killer cells were determined simultaneously by flow cytometry. Five of 12 nitroprusside-treated patients developed significant intraoperative increases of epinephrine levels (+69% versus preoperatively) which were not seen in the remaining seven patients. In these five patients, beta 2-receptor density of unfractionated lymphocytes was 26% lower (P < 0.05) on the first day after surgery compared with preoperative values. Since no changes in proportions of lymphocyte subpopulations were observed, these results are not caused by redistribution phenomena inducing a decrease of subsets with a high number of beta receptors. These findings suggest that beta 2-adrenergic responsiveness might be diminished after nitroprusside treatment in some patients.

Adrenergic beta-Antagonists↗
PubMed1976

Nitroprusside-induced cyanide poisoning: antidotal effect of hydroxocobalamin.

Sodium nitroprusside was investigated as a potential source of cyanide poisoning, Whole-blood cyanide determinations were performed on arterial samples from baboons receiving nitroprusside while anesthetized. There was a statistically significant increase in cyanide levels, as well as development of tachyphylaxis and severe metabolic acidosis. Hydroxocobalamin (vitamin B12a) infused simultaneously with nitroprusside significantly lessened the increase in cyanide levels and eliminated the development of metabolic acidosis. Nitroprusside can cause cyanide intoxication in the baboon, and hydroxocobalamin appears to be an effective antidote.

Acid-Base Equilibrium↗
PubMed1977

Canine systemic and cerebral effects of hypotension induced by hemorrhage, trimethaphan, halothane, or nitroprusside.

In 62 dogs, hypotension to a mean arterial pressure of either 40 or 50 torr (equivalent to a cerebral perfusion pressure of 30 or 40 torr, respectively) for one hour was induced by hemorrhage (oligemia), trimethaphan, halothane, or sodium nitroprusside. Before and during the period of hypotension, the following were measured: mean arterial blood pressure, cardiac output, whole-body O2 consumption, cerebral blood flow, cerebral O2 consumption, arterial blood gases, blood O2 content, and lactate, pyruvate, glucose, epinephrine, and norepinephrine concentrations. At the end of the period of hypotension, brain biopsies were taken for determination of adenosine triphosphate, phosphocreatine, lactate, and pyruvate concentrations. In an additional eight dogs following one hour of hypotension (at 40 torr) induced by one of the four techniques, the brains were perfused with carbon black, removed, and examined. In another ten dogs following hypotension (at 40 torr) induced with either halothane or trimethaphan, the animals were observed for three days and then killed for examination of the brain. Dogs maintained at a mean arterial pressure of 40 torr, despite differences in cerebral blood flow, demonstrated metabolic disturbances compatible with systemic and cerebral hypoxia. These were greatest in those dogs given nitroprusside in excess of 1.0 mg/kg, presumably due to cyanide toxicity. In dogs maintained at 50 torr, metabolic disturbances were minimal or absent in the halothane- and nitroprusside-treated dogs but were still apparent in the oligemic and trimethaphan-treated dogs. Carbon black infusions revealed no evidence of non-homogeneous flow. Three of the ten dogs observed for three days had persistent post-hypotension neurologic dysfunction. Two of these were given trimethaphan. The results suggest that the systemic and cerebral effects of halothane and nitroprusside (at doses less than 1.0 mg/kg) are similar and at a mean arterial pressure of 50 torr are of little consequence. By contrast, hypotension induced by trimethaphan or oligemia results in detectable metabolic alterations even at a pressure of 50 torr.

Adenosine Triphosphate↗
PubMed1979

Hypertension during anesthesia on discontinuation of sodium nitroprusside-induced hypotension.

The authors had observed that on intraoperative discontinuation of sodium nitroprusside being administered to induce hypotension, mean arterial pressure increased to above the pre-hypotension level. Twelve patients who recieved hypotensive anesthesia for surgical correction of cerebral aneurysms were studied to evaluate the role of the renin-angiotensin system in this phenomenon. In the awake state, mean arterial pressure was 100 +/- 2 torr and plasma renin activity 3.0 +/- 0.1 ng/ml/hr. Thirty minutes after the establishment of stable halothane-nitrous oxide anesthesia, mean arterial pressure decreased to 85 +/- 1 torr and plasma renin activity increased to 4.4 +/- 0.1 ng/ml/hr. No appreciable change in either occurred over the next two hours of operation. During sodium nitroprusside-induced hypotension, mean arterial pressure decreased to 49 +/- 2 torr and plasma renin activity increased to 15.2 +/- 0.2 ng/ml/hr. Thirty minutes after discontinuation of sodium nitroprusside administration, mean arterial pressure increased to 112 +/- 2 torr, which was not only higher than the prehypotension level, but also significantly higher than that recorded in the awake state. Plasma renin activity at that time was 10.9 +/- 0.1 ng/ml/hr. As the half-life of plasma renin is 15 min, the data suggest that the persistently increased plasma renin activity is probably responsible for the increase of arterial pressure following sodium nitroprusside-induced hypotension.

Adolescent↗
PubMed1982

Combined effects of sodium nitroprusside and propranolol on hypoxic pulmonary vasoconstriction.

Recent clinical experience and previous experimental work indicate that propranolol may reverse sodium-nitroprusside-induced inhibition of hypoxic pulmonary vasoconstriction (HPV). Accordingly, the authors decided to test this possibility in an experimental model that allows direct examination of pharmacologic influence on HPV. Six mongrel dogs were anesthetized with pentobarbital and intubated. Following a left thoracotomy, the left lower lobe (LLL) was ventilated independently but synchronously with the rest of the lung. Selective hypoxia of the LLL (95% nitrogen and 5% CO2) caused a 59 +/- 6% (mean +/- SE) decrease in the electromagnetically measured fraction of the cardiac output perfusing the LLL and a 287 +/- 65% increase in the pulmonary vascular resistance of the LLL from their respective prehypoxic values. Propranolol, 1 mg/kg intravenously, caused a 76 +/- 5% beta-blockade, as determined by an isoproterenol infusion test, but did not cause a significant change in the LLL HPV response. Sodium nitroprusside (SNP) infusion, caused a 38 +/- 4% decrease in systemic arterial pressure, and nearly abolished LLL HPV. Most important, the addition of propranolol to sodium nitroprusside did not significantly change the SNP induced inhibition of LLL HPV. The authors conclude that in acute lung disease, propranolol does not alter lobar HPV and does not reverse sodium nitroprusside inhibition of lobar HPV.

Animals↗
PubMed1983

Plasma renin, catecholamine, and vasopressin during nitroprusside-induced hypotension in ewes.

The effect of acute nitroprusside-induced hypotension on plasma renin activity, catecholamine, and vasopressin concentrations was examined in eight chronically catheterized, conscious ewes. Nitroprusside was infused intravenously for one hour at rates adjusted to achieve a 20% decrease in mean blood pressure (dose range: 14-50 mg, or about 5.8-18.5 micrograms X kg-1 X min-1). During hypotension, renin activity increased from 1.39 +/- 0.49 to 3.92 +/- 1.38 ng X ml-1. h-1, catecholamine concentrations remained unchanged, and vasopressin increased from 1.7 +/- 0.4 to 110 +/- 52.7 pg/ml. A significant positive correlation was obtained between total nitroprusside dose and peak vasopressin level (r = 0.749, P = 0.015). No significant change in arterial-blood pH, PO2, PCO2, plasma osmolality, or sodium concentration were observed throughout the experiment, thus eliminating the possibility of osmolar or hypoxic stimuli for the increased renin activity and vasopressin release. The magnitude of vasopressin release found in our studies implies that it plays a more important role than renin in defense against acute hypotension. In addition, the authors experiments suggest that variation in vasopressin release may be responsible for the variation of the dose of nitroprusside required to maintain hypotension.

Animals↗
PubMed1989

Intravenous labetalol versus sodium nitroprusside for treatment of hypertension postcoronary bypass surgery.

Hypertension is common following coronary artery bypass surgery. The safety of labetalol, a recently released combined alpha-1 and beta-adrenergic blocking agent for treatment of hypertension in this clinical situation is controversial. The authors compared the hemodynamic effects of labetalol with those of sodium nitroprusside (SNP) in 91 patients with good left ventricular function and equally severe coronary artery disease and in whom coronary artery bypass surgery had been just completed. They were anesthetized using fentanyl, diazepam, and enflurane. If hypertension developed postoperatively, patients were randomized to receive labetalol, 2 mg/min to a maximum of 300 mg (20 patients) or sodium nitroprusside in 0.5 micrograms.kg-1.min-1 increments by infusion (20 patients) to return blood pressure to normal. Compared with control values, labetalol brought about significant (P less than 0.05) reductions in heart rate, and cardiac index. No change was noted in stroke volume or systemic vascular resistance, but slight increases were found in central venous pressure and pulmonary capillary wedge pressure. Sodium nitroprusside treatment caused significant increases in heart rate and cardiac index while reducing diastolic blood pressure, central venous pressure, and pulmonary capillary wedge pressure. Stroke volume remained unchanged. Following the study period, blood pressure was controlled in all patients with SNP. Total doses of SNP in the 16 h following the study period were significantly less in the labetalol group (46.6 +/- 11.7 mg) versus (116.1 +/- 10.3 mg) in the SNP group (P less than 0.05). In this clinical circumstance, labetalol can be safe and effective for controlling hypertension, but its mechanism of achieving this effect varies from that for sodium nitroprusside.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2002

The influence of hyperoxic ventilation during sodium nitroprusside-induced hypotension on skeletal muscle tissue oxygen tension.

BACKGROUND: Increasing inspired oxygen concentrations might provide a simple and effective intervention to increase oxygen tension in tissues during controlled hypotension. To test this hypothesis, the influence of hyperoxic ventilation (100% O2) on skeletal muscle oxygen partial pressure (Ptio2) in patients receiving sodium nitroprusside-induced controlled hypotension was studied. METHODS: Forty-two patients undergoing radical prostatectomy were prospectively studied and randomly divided into three groups as follows: (1) Controlled hypotension induced by sodium nitroprusside (mean arterial blood pressure, 50 mmHg) and hyperoxic ventilation (CH-100%; n = 14); (2) controlled hypotension and ventilation with 50% O2 in nitrous oxide (CH-50%; n = 14); and (3) standard normotensive anesthesia with 50% O2 in nitrous oxide (control; n = 14). Ptio2 values were measured continuously in all patients using implantable polarographic microprobes. Arterial blood gases and lactate concentrations were analyzed in 30-min intervals. RESULTS: Surgical blood loss and transfusion requirements were significantly reduced in both groups receiving hypotensive anesthesia. During surgery, arterial partial pressure of oxy-gen and arterial oxygen content were significantly higher in patients of the CH-100% group. Baseline values of Ptio2 were comparable between the groups (CH-50%: 25.0 +/- 0.7 mmHg; CH-100%: 25.2 +/- 0.2 mmHg; control: 24.5 +/- 0.2 mmHg). After a transient increase in Ptio2 in the CH-100% group during normotension, Ptio2 values returned to baseline and remained unchanged in the control group. Ptio2 decreased significantly during the hypotensive period in the CH-50% group. The lowest mean Ptio2 values were 15.0 +/- 4.1 mmHg in the CH-50% group, 24.2 +/- 4.9 mmHg in the CH-100% group, and 23.5 +/- 3.8 mmHg in the control group. There were no significant changes in lactate plasma concentrations in any group throughout the study period. CONCLUSIONS: Hyperoxic ventilation improved skeletal muscle tissue oxygenation during sodium nitroprusside-induced hypotension. This improved local tissue oxygenation seems to be most likely due to an increase in convective oxygen transport and the attenuation of hyperoxemia-induced arteriolar vasoconstriction by sodium nitroprusside.

Aged↗
PubMed1991

Influence of infusion pumps on the pharmacologic response to nitroprusside.

OBJECTIVE: To compare the relationship between variability in nitroprusside delivery from five infusion pumps and the resulting variability in mean arterial pressure (MAP). DESIGN: Randomized, crossover study design. SETTING: A pediatric ICU in a university hospital. PATIENTS: Informed parental consent was obtained for six patients who were hemodynamically stable and receiving a continuous nitroprusside infusion for a clinical application. Subjects ranged in age from 11 months to 9 yr. INTERVENTIONS: All of the subjects were administered nitroprusside using selected infusion pumps, which included Abbott (Micro), 3M/AVI (210), IMED (965), IVAC (565), and Kendall McGaw (MicroRate). MEASUREMENTS AND MAIN RESULTS: After an initial equilibration interval for each device, MAP was measured and recorded at 10-sec intervals for greater than or equal to 90-min intervals using a computerized data collection technique. Variation in nitroprusside administration (flow continuity) for each infusion pump was determined in vitro using a computerized gravimetric technique. Variation in both MAP and flow continuity was mathematically expressed as the coefficient of variance (CV) of the measured values for each of the respective infusion pumps. For the Abbott, IMED, 3M/AVI, IVAC, and Kendall McGaw, infusion pumps, mean +/- SD continuity CV values were 85 +/- 31%, 39 +/- 26%, 19 +/- 8%, 17 +/- 3%, and 12 +/- 3%, respectively, and MAP CV values were 18 +/- 21%, 15 +/- 11%, 8 +/- 2%, and 16 +/- 10%, respectively. CONCLUSIONS: An apparent direct relationship between MAP variability and flow continuity was observed. We speculate that variation in effect of potent short-acting drugs may, in part, be due to infusion pump operation.

Blood Pressure↗
PubMed1993

Inhibition by nitroprusside of platelet calcium mobilization: evidence for reduced sensitivity to nitric oxide in essential hypertension.

OBJECTIVE: Although platelets from patients with moderate hypertension are abnormally sensitive to agonist-induced aggregation, their sensitivity to antagonists is not known. Nitric oxide (NO) is an endogenous antagonist of platelet function. The objective of this study was to determine whether platelet sensitivity to the inhibitory activity of sodium nitroprusside, a donor of NO, is abnormal in hypertension. DESIGN AND METHODS: Untreated patients with uncomplicated essential hypertension (mean arterial pressure > 120 mmHg) were studied. The rise in cytosolic calcium in response to 9,11-deoxy-11 alpha, 9 alpha-epoxymethanoprostaglandin F2 alpha (U46619, a thromboxane mimetic) was measured in fura-2-loaded platelets from 20 patients and 15 normotensive healthy subjects. Inhibition by sodium nitroprusside was measured in a further group of 14 patients and 20 normotensive subjects. RESULTS: Basal cytosolic calcium concentration and the rise in this parameter induced by U46619 were significantly greater in platelets from hypertensive patients than in those from normotensive controls. The mean half-maximal inhibitory concentration of nitroprusside to calcium mobilization induced by 3 mumol/l U46619 was 3.1-fold greater in platelets from hypertensive patients than in those from controls (95% confidence interval 1.6-6.0). CONCLUSION: The sensitivity of platelets to nitroprusside is reduced in essential hypertension. This reduced sensitivity to NO might influence the risk of arterial thrombosis in hypertensives.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMedDate not supplied

Hemodynamic consequences of administration of phentolamine or nitroprusside with dopamine in the dog.

Dopamine was administered intravenously to two groups of anesthetized dogs at rates of 2.5, 5, 10 and 20 micrograms/kg/min. After the 20 micrograms/kg/min infusion, mean arterial pressure, heart rate, renal blood flow, mean pulmonary arterial pressure, and left ventricular filling pressure were increased. The dopamine infusion was continued in both groups of animals. In Group I phentolamine was administered at rates of 2.5, 5, and 7.5 micrograms/kg/min; in Group II sodium nitroprusside at rates of 1, 2, 3, and 4 micrograms/kg/min. Phentolamine and sodium nitroprusside produced similar reductions in mean arterial blood pressure, mean pulmonary arterial pressure, left ventricular filling pressure, and similar increments in heart rate. Renal blood flow was maintained with phentolamine infusions and decreased slightly with the nitroprusside infusions. These studies demonstrated that both phentolamine and nitroprusside have the ability to reduce the vasoconstricting effects of dopamine.

Animals↗
PubMedDate not supplied

Comparison of the cardiovascular actions of N,N-di-n-propyl dopamine and sodium nitroprusside in conscious and chloralose-anaesthetised dogs.

The cardiovascular actions of N,N-Di-n-propyldopamine (DPDA), a dopamine receptor agonist, and the directly acting vasodilator sodium nitroprusside have been compared in both conscious and chloralose-anaesthetised dogs. Bolus intravenous doses of DPDA (6.5-32 micrograms/kg) and sodium nitroprusside (3-10 micrograms/kg) induced dose-related falls in blood pressure associated with reflex tachycardia in both preparations. The dopamine receptor antagonist sulpiride (0.5 mg/kg) eliminated these effects of DPDA and its ability to reduce renal and femoral vascular resistances in the chloralose-anaesthetised dog, but did not influence the actions of sodium nitroprusside. Ganglion blockade (hexamethonium, 5-10 mg/kg alone or in a combination with atropine, 1 mg/kg) abolished the reflex tachycardia to both compounds and potentiated the depressor effects of sodium nitroprusside but either reduced or did not alter the hypotension produced by DPDA. The renal dilator response to DPDA was also reduced, while femoral vasodilation was abolished. This study illustrates that DPDA can reduce blood pressure in conscious and chloralose-anaesthetised dogs but that this effect is accompanied by reflex tachycardia. Inhibitory dopamine receptors on sympathetic nerves, and to a lesser extent postjunctional (vascular) dopamine receptors, are involved in these actions of DPDA.

Anesthesia↗
PubMed1991

Interactions between isoprenaline, sodium nitroprusside, and isozyme-selective phosphodiesterase inhibitors on ADP-induced aggregation and cyclic nucleotide levels in human platelets.

The interactions between isoprenaline, sodium nitroprusside, and the isozyme-selective phosphodiesterase inhibitors OPC 3911 ("cAMP specific") and zaprinast ("cGMP specific") on platelet aggregation induced by adenosine diphosphate (ADP) and on levels of cAMP and cGMP were studied. Isoprenaline at 10(-6)M diminished aggregation by 28%, and this effect was enhanced by 10(-7)-10(-6)M OPC 3911. Neither 10(-6) M isoprenaline nor 10(-7)M OPC 3911 elevated cAMP, but in combination they caused a significant rise in cAMP (27% above the basal level), accompanying the synergistic functional inhibition, without affecting cGMP levels. Sodium nitroprusside at 10(-5) M diminished aggregation by 39%, elevated cGMP levels (81-110%), but also caused a statistically significant increase in cAMP (21-32%), and enhanced the effects of 10(-6)M isoprenaline on cAMP levels. Zaprinast at 10(-5) M caused a modest inhibition of aggregation by 20%, and a small increase in cGMP (20%), and it clearly enhanced the effects of 10(-5)M sodium nitroprusside on both cGMP and cAMP levels, but not on aggregation. The cAMP-increasing effect of sodium nitroprusside might be a consequence of a cGMP-mediated inhibition of the "low-Km cGMP-inhibited phosphodiesterase" that is also inhibited by OPC 3911. The effects of all of the drugs on ADP-induced aggregation seem to depend more on their effect on cAMP levels than on the levels on cGMP.

Cyclic AMP↗