Platelet cyclic GMP responses to nitroglycerin.
The present study further investigates the use of platelet cyclic guanosine monophosphate (GMP) as a biochemical measure of tolerance. Platelet cyclic GMP has been reported as a marker of the biochemical effects of nitroglycerin (GTN) and as an indicator of the development of tolerance. Platelet cyclic GMP levels and systolic blood pressure (SBP) were measured repeatedly in nine subjects who received continuous transdermal GTN therapy (0.6 mg/hour), and in nine control subjects who did not. These measurements were also made before and after sublingual GTN (0.6 mg) in both groups. Whole blood from five subjects was incubated with normal saline (as a control), with 22 nM GTN (representing a therapeutic GTN concentration), and with 100 microM GTN. Although the acute administration of transdermal GTN caused a significant decrease in SBP (112 +/- 3 to 96 +/- 3 mmHg, p = 0.003), SBP returned to baseline following 1 week of continuous therapy. Platelet cyclic GMP levels did not change in response to transdermal GTN, either acutely or following sustained therapy. Similarly, sublingual GTN caused no change in platelet cyclic GMP in either group. There was no change in platelet cyclic GMP concentration following incubation with 22 nM GTN. Platelet cyclic GMP did increase following incubation with 100 microM GTN (0.883 +/- 0.043 pmol/10(9) platelets, p < 0.001). These results demonstrate that platelet cyclic GMP levels do not change in response to clinically relevant doses of GTN. Literature supporting the use of platelet cyclic GMP levels as an index of GTN effects and/or tolerance should be interpreted with caution.
Martin
D D
DD
Department of Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
Tong
J S
JS
Parker
J D
JD
D000279:Administration, Cutaneous; D000286:Administration, Sublingual; D000328:Adult; D000704:Analysis of Variance; D001792:Blood Platelets / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D006152:Cyclic GMP / Q000097:blood*; D006801:Humans; D008297:Male; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology*
D005996:Nitroglycerin; D006152:Cyclic GMP