Platelet cyclic GMP. A potentially useful indicator to evaluate the effects of nitroglycerin and nitrate tolerance.

Abstract

These results indicate that platelet cGMP can be used as an indicator for in situ evaluation of nitroglycerin effects and that patients who have received nitrates develop nitrate tolerance, which affects intracellular production of cGMP and vasodilation in the response to nitroglycerin.

Parallel tolerance between platelet cyclic GMP and preload effects of nitroglycerin in anaesthetized mini‐pigs

“…Kukovetz & Holzmann (1986) showed that the in vitro exposure of vascular tissue to NTG caused a dose-related increase in intracellular cyclic GMP which correlated with the simultaneous relaxation of the preparation, with both effects being impaired after prolonged incubation with NTG. Similar findings were reported in vivo (Watanabe et al, 1993) where the increase in platelet cyclic GMP correlated with epicardial coronary artery diameter. Both platelet cyclic GMP and the coronary artery changes were less pronounced in those patients receiving nitrate therapy.…”

“…and although they do not appear to possess the enzyme required for the direct conversion of NTG, it is believed that sufficient NO can be released from NTG by the vascular tissue enzyme to enable activation of the platelet guanylate cyclase (Gerzer et al, 1989). Thus platelet cyclic GMP might be an index of the tone, or state of relaxation of the vessels (Watanabe et al, 1993;Fung et al, 1993) following intravenous NTG.…”

“…Arterial blood samples were withdrawn prior to and 1 min following each infusion. Cyclic GMP was extracted according to Watanabe et al (1993) and the aqueous phase analysed using a [3H]-cyclic GMP radioimmunoassay kit (Amersham). All data were calculated as the mean ± s.e.mean.…”

Efficacy and Rebound Phenomenon Related To Intermittent Nitroglycerin Therapy for the Prevention of Nitrate Tolerance

“…We previously reported that there was a good correlation between the percent increase in platelet cGMP level and the percent dilatation of coronary arteries, and that the intracellular production of platelet cGMP level was decreased during continuous nitrate therapy. 8 These observations suggest that nitrate tolerance is related to blunted vasodilation due to the attenuation of intracellular production of cGMP in response to NTG. Parker et al suggested that nitrate therapy is associated with both neurohormonal activation and plasma volume expansion and that these responses may play a role in the loss of nitrate efficacy.…”

“…The pellet was suspended in modified Tyrode's solution (containing 0.35% bovine serum albumin and 5 mmol/L HEPES, pH 7.35) to obtain a final platelet count of 2-3×10 6 platelets/ l. Samples were stored frozen at -70°C until analysis. 8 …”