Effects of an oral dose of isosorbide dinitrate on platelet function and fibrinolysis in healthy volunteers.

Abstract

1. A randomised double‐blind placebo‐controlled study was performed to investigate the effects of isosorbide dinitrate (ISDN; 20 mg orally) on various aspects of platelet function and fibrinolysis in vivo in 12 healthy volunteers. 2. Measurements were performed at rest (before and after tablet ingestion) and during platelet activation by adrenaline (0.4 nmol kg‐1 min‐1; 30 min infusion). 3. At rest, ISDN did not alter plasma concentrations of beta‐thromboglobulin (beta TG). EC50 values for ADP induced aggregation in vitro (Born aggregometry) or ex vivo filtragometry readings. Adrenaline markedly increased platelet aggregability in vivo as measured by filtragometry and elevated levels of beta TG in plasma. ISDN treatment did not affect these responses in the group as a whole. 4. Individuals responding to ISDN with more pronounced vasodilatation at rest showed a lesser increase in aggregability during the ensuing adrenaline infusion (r = ‐0.66, P = 0.02) despite higher adrenaline levels during ISDN. In individuals showing a significant decrease in systolic blood pressure (n = 8) ISDN tended to attenuate the adrenaline induced increase in platelet aggregability (filtragometry; P = 0.08), despite higher plasma adrenaline and noradrenaline levels after ISDN ingestion. 5. Plasma concentrations of ISDN and its active metabolites isosorbide‐5‐ mononitrate and isosorbide‐2‐mononitrate were not correlated to haemodynamic or platelet variables. 6. Fibrinolytic activity (t‐PA antigen and activity, PAI‐1 antigen and activity) increased similarly during the adrenaline infusion following ISDN and placebo. 7. It is concluded that ISDN may affect platelet aggregation responses to adrenaline in vivo, but only in individuals showing significant haemodynamic responses to ISDN.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of treatment with oral isosorbide dinitrate on platelet function in vivo; a double‐blind placebo‐controlled study in patients with stable angina pectoris.

“…In contrast to our findings in healthy volunteers [12], there were no relationships between ISDN induced vasodilation (i.e. the decrease in systolic blood pressure at rest, calculated as placebo values minus ISDN values) and the filtragometry readings-either at rest or during platelet activation by exercise (the platelet activating effect was expressed either as the percent decrease in tA (exercise divided by rest), or the corresponding algebraic difference (i.e.…”

“…On the other hand, platelet function is complex and platelet attenuating effects of nitrates may not be revealed with insensitive in vitro techniques or when measurements are performed only at rest. In healthy volunteers ISDN tended to attenuate platelet responses in vivo to adrenaline infusion, without any effect in the basal state [12].…”

“…Such effects increased support [8]. It should, however, be realized Correspondence: Dr Paul Hjemdahl, Department of Clinical Pharmacology, Karolinska Hospital, S-17176 Stockholm, Sweden that there are few controlled studies on the matter, and that several investigators have been unable to document significant platelet inhibition after nitrate administration [9][10][11][12]. On the other hand, platelet function is complex and platelet attenuating effects of nitrates may not be revealed with insensitive in vitro techniques or when measurements are performed only at rest.…”

Altered Interaction Between Plasminogen Activator Inhibitor Type 1 Activity and Sympathetic Nerve Activity With Aging

“…14,32,33 Recent observations are that fibrinolysis with tPA activity, tPA antigen and PAI-1 activity depend on catecholamine levels. 24,[34][35][36][37] A previous report suggested that non-selective -blockers abolished fibrinolytic activity mediated by epinephrine. 38 Our results show that SNA is significantly related to PAI-1 activity during LBNP, which suggests that PAI-1 activity would be increased by enhanced sympathetic efferent neuronal activity.…”

“…LBNP is well known to increase SNA and catecholamine concentration by reducing baroreceptor restraint. 41,42 Previous results suggest that dose-dependent stimulation with an infusion of epinephrine increases PAI-1 activity within 15-40 min, 35 which suggests that elevation of catecholamine levels or orthostatic stress induces a hypercoagulable state. However, the measurement of catecholamine levels is largely influenced by factors such as posture and mental stress, so we evaluated direct recording of efferent SNA, which enables an exact response of SNA to be measured during physiological stress.…”