Persistent inhibition of platelets during continuous nitroglycerin therapy despite hemodynamic tolerance.
BACKGROUND
Nitroglycerin has been shown to possess antiplatelet properties in both animals and humans. Tolerance to the hemodynamic effects of nitroglycerin develops with continuous therapy, but it is unclear whether there is tolerance to its antiplatelet effect.


RESULTS
Tolerance to nitroglycerin was studied by exposing porcine aortic media to flowing arterial blood from control pigs (n = 9) or pigs treated with continuous nitroglycerin patches (Nitro-dur, 0.8 mg/h; n = 11) at a shear rate of 3397 s-1 for 3 minutes. Relative to baseline, mean arterial pressure fell by approximately 10% at 3 and 24 hours (P < .05) but returned to baseline at 48 hours of continuous nitroglycerin treatment, whereas no significant changes were observed in control animals. Autologous 51Cr-labeled platelet deposition (x 10(6)/cm2) on the aortic media at baseline and 3, 24, and 48 hours remained stable in control animals, with mean values of 94.8 +/- 5.9, 89.4 +/- 8.3, 89.3 +/- 8.8, and 84.3 +/- 5.7, respectively. However, in pigs treated continuously with nitroglycerin for 48 hours, platelet deposition was reduced significantly at 3 (65.9 +/- 4.8), 24 (63.8 +/- 6.4), and 48 hours (56.5 +/- 7.3) of nitroglycerin treatment compared with baseline (93.1 +/- 3.6). Platelet aggregation induced by thrombin also decreased at 3 (12.4 +/- 1.3), 24 (12.6 +/- 1.7), and 48 hours (10.8 +/- 1.6) of nitroglycerin treatment compared with baseline (16.3 +/- 1.4) but remained unchanged in the control group. Also, nitroglycerin treatment increased intraplatelet cGMP at 3, 24, and 48 hours compared with baseline.


CONCLUSIONS
This study demonstrates the persistent inhibition of platelet function and platelet deposition on an injured arterial wall by continuous nitroglycerin therapy despite hemodynamic tolerance.
Hébert
D
D
Department of Medicine, Montreal Heart Institute, University of Montreal Medical School, Canada.
Xiang
J X
JX
Lam
J Y
JY
D000279:Administration, Cutaneous; D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000097:blood; D004361:Drug Tolerance; D006439:Hemodynamics / Q000187:drug effects*; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors; D013552:Swine; D013997:Time Factors; D017540:Tunica Media / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; D005996:Nitroglycerin; D006152:Cyclic GMP