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 (O2-) content. Angiotensin II (Ang II) has been shown to augment O2- formation. Recent studies have demonstrated that angiotensin-(1-7) [Ang-(1-7)] has opposite actions to those of Ang II in the vasculature. This study compares the effects of Ang-(1-7) and Ang II on platelet aggregation and platelet responsiveness to the NO donor sodium nitroprusside (SNP). Platelet aggregation was induced by the thromboxane A2 mimetic U46619 (1-5 micromol/L), and the inhibitory effects of SNP (10 micromol/L) on the rate and extent of aggregation were quantified. Ang II 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.
Rajendran
Sharmalar
S
Cardiology Unit, The Queen Elizabeth Hospital, The University of Adelaide, S.A., Australia.
Chirkov
Yuliy Y
YY
Campbell
Duncan J
DJ
Horowitz
John D
JD
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology; D003327:Coronary Disease / Q000097:blood; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000097:blood; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D020030:Nitric Oxide Donors; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009599:Nitroprusside; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000803:Angiotensin I; C118790:angiotensin I (1-7)