Angiotensin-(1-7) enhances anti-aggregatory effects of the nitric oxide donor sodium nitroprusside

Patients with ischemic heart disease have platelets that are resistant to the anti-aggregatory effects of nitric oxide (NO) donors. This NO resistance is associated with increased whole blood superoxide radical (O-2(-)) content. Angiotensin II (Ang II) has been shown to augment O-2(-) formation. Recent studies have demonstrated that angiotensin-(1-7) [Ang-(1-7)] has opposite actions to those of Ang 11 in the vasculature. This study compares the effects of Ang(1-7) and Ang 11 on platelet aggregation and platelet responsiveness to the NO donor sodium nitroprusside (SNP). Platelet aggregation was induced by the thromboxane A(2) mimetic U46619 (1-5 mu mol/L), and the inhibitory effects of SNP (10 mu mol/L) on the rate and extent of aggregation were quantified. Ang 11 did not induce aggregation, but 10-100 nmol/L Ang II potentiated U46619-induced aggregation by 21 +/- 6% in the absence and by 26 +/- 9% in the presence of SNP (P < 0.01 for both), in blood samples from 8 normal subjects. By contrast, Ang-(1-7) alone did not affect platelet aggregation, but 10-100 nmol/L Ang-(1-7) potentiated the anti-aggregatory effects of SNP in blood samples from both normal subjects (n = 17) and patients with acute coronary syndromes (n = 17). This effect of Ang(1-7) was bimodal, and at higher concentrations of Ang-(1-7), potentiation was abolished. The maximum incremental effects of Ang-(1-7) on inhibition of aggregation were 25 +/- 4% and 28 +/- 5%, for rate and extent of aggregation respectively (P < 0.01 for both), corresponding to a 2.3-fold potentiation of the anti-aggregatory effect of SNP. Platelets from patients were resistant to the anti-aggregatory effect of SNP, but potentiation of SNP effects by Ang-(1-7) was similar for patients and normal subjects. Thus, Ang-(1-7) potentiates the anti-aggregatory effects of NO donor, and may therefore counteract platelet NO resistance that accompanies cardiovascular disease.