Reduced platelet aggregability and increased vascular prostacyclin formation in a variant rat strain (IVA-SIV) with endogenous hypertriglyceridemia.
The Ivanovas-Sieve (IVA-SIV) rat represents the only available animal model of endogenous hypertriglyceridemia, in the absence of obesity and/or overt diabetes. Since plasma lipids/lipoproteins can modulate platelet reactivity and eicosanoid metabolism, these were examined in two groups of Charles River (CR) and IVA-SIV rats of identical age. The IVA-SIV rats had 2-fold higher plasma triglycerides and a 55% higher number of circulating platelets; the number of platelets was significantly correlated with triglyceridemia. Platelet reactivity to ADP and to collagen was significantly reduced in these animals, whereas the formation of thromboxane B2 did not differ from that of the CR. After perfusion of platelet-rich plasma (PRP) through the aortas of animals of the two strains, platelet aggregability, already lower in the IVA-SIV, was reduced to a higher extent compared to the CR. Increased levels of the prostacyclin metabolite 6-keto-PGF1 alpha were identified in the perfusate from the aortas of IVA-SIV rats. Platelets from these animals also showed an increased sensitivity to Iloprost, a stable prostacyclin analogue, with an IC50 1.7-fold lower compared to CR rats. Spontaneous hypertriglyceridemia in the IVA-SIV model is not associated with platelet hyperresponsiveness, but rather with a reduced sensitivity to major aggregants.
Lovati
M R
MR
Department of Pharmacology, University of Milan, Italy.
Manzoni
C
C
Mosconi
C
C
Colli
S
S
Sirtori
C R
CR
Fumagalli
G
G
Clementi
F
F
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood*; D000818:Animals; D001013:Aorta, Thoracic; D015228:Hypertriglyceridemia / Q000097:blood*; D008297:Male; D010477:Perfusion; D010974:Platelet Aggregation; D010976:Platelet Count; D051381:Rats; D011919:Rats, Inbred Strains; D013929:Thromboxane B2 / Q000097:blood*; D014280:Triglycerides / Q000097:blood
D014280:Triglycerides; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha