Nitrate resistance in platelets from patients with stable angina pectoris.
BACKGROUND
Hemodynamic resistance to nitrates has been previously documented in congestive heart failure. In patients with stable angina pectoris (SAP), we have observed a similar phenomenon: decreased platelet response to disaggregating effects of nitroglycerin (NTG) and sodium nitroprusside (SNP).


RESULTS
In blood samples from normal subjects (n=32) and patients with SAP (n=56), we studied effects of NO donors (NTG and SNP) on ADP-induced platelet aggregation and on intraplatelet cGMP. NTG and SNP inhibited platelet aggregation in patients to lesser extents than in normal subjects (P<0.01). The cGMP-elevating efficacy of NTG and SNP was diminished in platelets from patients in comparison with those from normals (P<0.001). Inhibition of the anti-aggregatory effects of NTG and SNP by ODQ, a selective inhibitor of NO-stimulated guanylate cyclase, was significantly less pronounced in patients than in normal subjects. Content of O2- was higher in blood samples from patients than in those from normal subjects (P<0. 01). In blood samples from patients with SAP, but not in normal subjects, the O2- scavenger superoxide dismutase (combined with catalase) suppressed platelet aggregation (P<0.01) and increased the extent of anti-aggregatory effect of SNP (P<0.01).


CONCLUSIONS
In patients with SAP, platelets are less responsive to the anti-aggregating and cGMP-stimulating effects of NO donors; this may reflect both reduction in guanylate cyclase sensitivity to NO and inactivation of the released NO by O2-. The implied impairment of anti-platelet efficacy of endogenous NO (in the form of EDRF) may contribute to platelet hyperaggregability associated with angina pectoris.
Department of Cardiology, The Queen Elizabeth Hospital, University of Adelaide, Australia.
Y Y
YY
Chirkov
A S
AS
Holmes
L P
LP
Chirkova
J D
JD
Horowitz
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000097:blood*; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology*; D004351:Drug Resistance / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D012016:Reference Values
D009566:Nitrates; D020030:Nitric Oxide Donors; D010975:Platelet Aggregation Inhibitors; D009599:Nitroprusside; D000244:Adenosine Diphosphate; D005996:Nitroglycerin