Inhibition of platelet aggregation by putrescine, spermidine, and spermine in hypercholesterolemic rabbits.
BACKGROUND
Hypercholesterolemia causes alterations in platelet function. Platelet hyperaggregation is considered a predisposing factor for atherosclerosis. In this paper, the antiaggregating effect of the polyamines putrescine, spermidine, and spermine was studied on platelets of normal and hypercholesterolemic rabbits.


METHODS
New Zealand rabbits were fed with a cholesterol-enriched diet for 10 weeks. Lipids and glucose were determined in serum. The assays of platelet aggregation were carried out using platelet-rich plasma (PRP) obtained from both control and cholesterol-fed rabbits. We used 2.5 micromol /mL ADP and 2 microg/mL collagen as inductors of platelet aggregation. In addition, arginase activity and L-arginine content were determined in PRP.


RESULTS
Serum total cholesterol and LDL-cholesterol concentrations were increased from 26.3 +/- 8.1 to 1,485.0 +/- 26.8 mg/dL and from 15.9 +/- 5.9 to 1,383.8 +/- 58.9 mg/dL, respectively, whereas triglyceride concentration increased from 88.3 +/- 35.6 to 411.0 +/- 154.5 mg/dL upon cholesterol feeding. Seventy-five percent of platelet aggregation inhibition was observed with 10 microM of polyamines in PRP of normal rabbits. Spermine inhibited platelet aggregation by 54% in PRP of hypercholesterolemic rabbits when ADP was used as agonist. The order of polyamine action was spermine > spermidine > putrescine. In addition, we found that platelet arginase activity and L-arginine content were unaltered upon hypercholesterolemia.


CONCLUSIONS
These results show that the polyamines putrescine, spermidine, and spermine have antagonist action in platelet aggregation and suggest a key role of polyamines in platelet aggregation under normal and hypercholesterolemic conditions.
Unidad de Investigación Médica en Enfermedades Metabólicas, Mexico City, Mexico.
N C
NC
de la Peña
J A
JA
Sosa-Melgarejo
R R
RR
Ramos
J D
JD
Méndez
D000818:Animals; D001119:Arginase / Q000097:blood; D001120:Arginine / Q000097:blood; D001161:Arteriosclerosis / Q000209:etiology / Q000517:prevention & control; D001786:Blood Glucose / Q000032:analysis; D001792:Blood Platelets / Q000737:chemistry / Q000201:enzymology; D001798:Blood Proteins / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000633:toxicity; D008078:Cholesterol, LDL / Q000097:blood; D004036:Diet, Atherogenic; D004353:Drug Evaluation, Preclinical; D006937:Hypercholesterolemia / Q000097:blood* / Q000150:complications; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011700:Putrescine / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D013095:Spermidine / Q000494:pharmacology / Q000627:therapeutic use*; D013096:Spermine / Q000494:pharmacology / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D001798:Blood Proteins; D002791:Cholesterol, Dietary; D008078:Cholesterol, LDL; D010975:Platelet Aggregation Inhibitors; D014280:Triglycerides; D013096:Spermine; D001120:Arginine; D002784:Cholesterol; D001119:Arginase; D013095:Spermidine; D011700:Putrescine