DO
PRODUCTS OF NITRIC OXIDE SYNTHASE CAUSE PLATELET HYPERAGGREGABILITY IN PATIENTS
WITH ANGINA PECTORIS? A.S.Holmes*,
M.Worthley, Y.Y.Chirkov, J.D.Horowitz The
Cardiology Unit, The Queen Elizabeth Hospital, Adelaide, South Australia. Platelets
from patients with stable angina pectoris (SAP) and unstable angina pectoris
(UAP) are hyper-aggregable and also hypo-responsive to the anti-aggregatory
effects of nitric oxide (NO). To date, the possible relationship between
hyper-aggregability and background activity of nitric oxide synthase (NOS), has
not been addressed previously. While it is conceivable that decreased NOS
activity might contribute to platelet hyper-aggregability, this would not be
expected to induce hypo-responsiveness to NO. We investigated the effects of
the non-specific NOS inhibitor L-NAME (300mM) (L-NG-nitroarginine
methyl ester) (10 minute pre-incubation) on the extent of ADP-induced (1mM) platelet aggregation in
whole blood from normal subjects (n=7) and patients with angina pectoris (n=20;
11 with SAP and 9 with UAP). Responses (inhibition of aggregation) to the NO
donor sodium nitroprusside (SNP 10mM) were also determined. Parameter
(Mean + SEM) Normal
Subjects Angina
Pectoris ADP-induced
aggregation SNP-induced *
p = 0.06 vs Control (Paired t-test), **
p = 0.02 vs Normal Subjects (Unpaired t-test), and # p < 0.01 vs Normal
Subjects (Unpaired t-test). In
both normal subjects (r = -0.8, p < 0.01) and patients (r = -0.6, p <
0.01), the percentage inhibition of platelet aggregation due to L-NAME was
inversely correlated with the response to SNP. Conclusions:
Effects of NOS inhibition on platelet aggregation vary between normal subjects
and patients with angina pectoris. A "paradoxical" anti-aggregatory effect in
some patients reflects a product of NOS other than NO (perhaps peroxynitrite);
that contributes to platelet hyper-aggregability. The anti-aggregatory effects
of L-NAME and the hypo-responsiveness to NO are strongly correlated, suggesting
a common basis for these phenomena.
(
)
Control
L-NAME
7.6+2.5
9.4+2.7*
9.3+1.3
8.3+1.1
aggregation with
L-NAME
()
1.9+0.8
-0.9+0.8**
inhibition
(%)
82+6
52+5 #
