The interaction of sodium nitroprusside with human endothelial cells and platelets: nitroprusside and prostacyclin synergistically inhibit platelet function

Journal Article · Wed Dec 01 04:00:00 EST 1982 · Circulation; (United States)

DOI:https://doi.org/10.1161/01.CIR.66.6.1299· OSTI ID:6374682

Levin, R I; Weksler, B B; Jaffe, E A

Sodium nitroprusside (NP) is a potent vasodilator that also inhibits platelet aggregation. To test the hypothesis that NP causes both of these effects by altering the balance between prostacyclin (PGI2) produced by endothelial cells and thromboxane A2 (TXA2) produced by platelets, we incubated each of these cell types with NP for 5 minutes and assayed the PGI2 and TXA2 produced. NP at pharmacologically achieved doses (0.01--30 micrograms/ml) inhibited platelet aggregation and resultant TXA2 synthesis in a dose- and time-dependent manner (p less than 0.001). The inhibition was not dependent on cAMP production, external calcium concentration, or suppression of TXA2 synthesis. NP did not alter the production of PGI2 by cultured human endothelial cells as measured by radioimmunoassay for 6-Keto-PGF1 alpha, the stable hydrolysis product of PGI2. However, supernates of NP-treated endothelial cells containing low, noninhibitory concentrations of NP unexpectedly inhibited platelet aggregation. This inhibition of platelet aggregation was due to synergy between PGI2 (0.1--3 nM) and NP (p interaction less than 0.03). The synergistic inhibition by NP and PGI2 of platelet aggregation and TXA2 synthesis in vivo may explain some of the beneficial actions of NP in the treatment of hypertension and congestive heart failure.

• Research Organization: Department of Medicine, New York University School of Medicine, New York
• OSTI ID: 6374682
• Journal Information: Circulation; (United States), Journal Name: Circulation; (United States) Vol. 66:6; ISSN CIRCA
• Country of Publication: United States
• Language: English

Related Subjects

560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMP
ANIMAL TISSUES
ANTIHYPERTENSIVE AGENTS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD PLATELETS
BODY
BODY FLUIDS
CARDIOVASCULAR AGENTS
DRUGS
DYNAMIC FUNCTION STUDIES
ENDOTHELIUM
ENZYME ACTIVITY
ENZYME INHIBITORS
ENZYMES
HEART FAILURE
KINETICS
MATERIALS
NUCLEOTIDES
ORGANIC COMPOUNDS
PHARMACOLOGY
REACTION KINETICS
SYMPTOMS
TISSUES