PARALLEL TOLERANCE BETWEEN PLATELET CYCLIC-GMP AND PRELOAD EFFECTS OFNITROGLYCERIN IN ANESTHETIZED MINIPIGS

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 e valuated in the anaesthetized mini-pig, using pressure-volume analysis . NTG (1-30 mu g kg(-1) min(-1), i.v.) elicited a dose-dependent fall in preload and afterload, and an increase in arterial blood platelet c yclic GMP. Repeated doses of NTG (30 mu g kg(-1) min(-1)) resulted in tolerance to the preload but not afterload effects. The increases in p latelet 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. Th e measurement of platelet cyclic GMP may represent a simple approach f or monitoring the degree of venous tolerance to NTG in animals or pati ents, facilitating further mechanistic investigations.