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 nitroglyce rin (GTN) and as an indicator of the development of tolerance. Platelet cyc lic GMP levels and systolic blood pressure (SBP) were measured repeatedly i n nine subjects who received continuous transdermal GTN therapy (0.6 mg/hou r), 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 f rom five subjects was incubated with normal saline (as a control), with 22 nM GTN (representing a therapeutic GTN concentration), and with 100 mu M GT N. Although the acute administration of transdermal GTN caused a significan t decrease in SEP (112 +/- 3 to 96 +/- 3 mmHg, p = 0.003), SEP 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 conc entration following incubation with 22 nM GTN. Platelet cyclic GMP did incr ease following incubation with 110 mu M GTN (0.883 +/- 0.043 pmol/10(9) pla telets, p < 0.001). These results demonstrate that platelet cyclic GMP leve ls do not change in response to clinically relevant doses of GTN. Literatur e supporting the use of platelet cyclic GMP levels as an index of GTN effec ts and/or tolerance should be interpreted with caution.