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

The effects of acute intravenous nitroglycerin (NTG) administration on platelet cyclic GMP in relation to changes in indices of preload (end-diastolic volume) and afterload (effective arterial elastance) were evaluated in the anaesthetized mini-pig, using pressure-volume analysis. NTG (1-30 micrograms kg-1 min-1, i.v.) elicited a dose-dependent fall in preload and afterload, and an increase in arterial blood platelet cyclic GMP. Repeated doses of NTG (30 micrograms kg-1 min-1) resulted in tolerance to the preload but not afterload effects. The increases in platelet cyclic GMP were also attenuated, being highly correlated with the preload changes. Therefore, platelet cyclic GMP appears to reflect NTG-induced venous tolerance, rather than arterial responsiveness. The measurement of platelet cyclic GMP may represent a simple approach for monitoring the degree of venous tolerance to NTG in animals or patients, facilitating further mechanistic investigations.