Potentiation of adrenaline-induced platelet aggregation by angiotensin II.
The effects of angiotensin II (ANG II) alone and in combination with other agonists on human platelet aggregation, thromboxane B2 (TxB2) and cytosolic [Ca2+]i were investigated. ANG II (10(-11) - 10(-7) M) alone had no direct effect on aggregation, TxB2 production or [Ca2+]i after short- (less than 2 min) or long-term (30 min) incubation. In contrast, low concentrations of ANG II (10(-11) M) enhanced adrenaline-induced platelet aggregation but high concentrations (10(-7) M) had an inhibitory effect. Moreover, ANG II (10(-11) - 10(-7) M) augmented platelet responses to the TxA2 mimetic, U44069. Pretreatment of platelets with flurbiprofen abolished this facilitatory effect of ANG II on adrenaline- but not on U44069-induced platelet aggregation. These results suggest that ANG II stimulation of agonist-induced platelet activation may be due to potentiation of the effects rather than the synthesis of TxA2.
D000804:Angiotensin II / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology*; D005480:Flurbiprofen / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011945:Receptors, Angiotensin / Q000502:physiology; D013929:Thromboxane B2 / Q000494:pharmacology
D011450:Prostaglandin Endoperoxides, Synthetic; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D013929:Thromboxane B2; C028429:U 44069; D005480:Flurbiprofen; D002118:Calcium; D004837:Epinephrine