caa a22 4500 475833627 CHVBK 20180406123847.0 cr unu---uuuuu 170329e20000601xx s 000 0 eng 10.1023/A:1007868317306 doi (NATIONALLICENCE)springer-10.1023/A:1007868317306 Platelet Cyclic GMP Responses to Nitroglycerin [Elektronische Daten] [Douglas Martin, Jeffrey Tong, John Parker] 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 μM 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 μM GTN (0.883 +/−0.043 pmol/109 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. Kluwer Academic Publishers, 2000 nitroglycerin nationallicence platelets nationallicence cyclic GMP nationallicence plethysmography nationallicence Martin Douglas Department of Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada aut Tong Jeffrey Department of Clinical Biochemistry, The Toronto Hospital, University of Toronto, Toronto, Ontario, Canada aut Parker John Department of Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada aut Cardiovascular Drugs and Therapy Kluwer Academic Publishers 14/4(2000-06-01), 419-425 0920-3206 14:4<419 2000 14 10557 https://doi.org/10.1023/A:1007868317306 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1007868317306 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Martin Douglas Department of Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada aut NATIONALLICENCE 700 1- Tong Jeffrey Department of Clinical Biochemistry, The Toronto Hospital, University of Toronto, Toronto, Ontario, Canada aut NATIONALLICENCE 700 1- Parker John Department of Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada aut NATIONALLICENCE 773 0- Cardiovascular Drugs and Therapy Kluwer Academic Publishers 14/4(2000-06-01), 419-425 0920-3206 14:4<419 2000 14 10557 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer