The Effect of Isosorbide Dinitrate on the Arterial Vascular Bed: A Dose Response Study in Dogs

Isosorbide dinitrate (ISDN) was infused stepwise intraarterially into the left hindlimb (5.7-364.8 micrograms/kg/min.) into six dogs. The mean local vascular resistance was decreased by 32% in the left hindlimb after a dose of up to 91.2 micrograms/kg/min. corresponding to a 1.6-fold increase in the left femoral artery blood flow, without significant changes in the control limb or central haemodynamics. The muscular blood flow in the adductor magnus muscle obtained by the Xenon washout technique remained unchanged in 6 of 7 other dogs at ISDN infusion rates of 91.2 micrograms/kg/min., indicating that the increase in femoral artery blood flow was not a consequence of increased muscular blood flow. The arterio-venous extraction fraction of radioactive microspheres was lower in the experimental leg during ISDN infusion when compared with the control leg, suggesting that AV-shunts are opened during ISDN infusion. In addition to the well-known effect on preload, the present results confirm that ISDN also acts on afterload. Thus, ISDN may be classified as a mixed agent acting on both pre- and afterload which is in agreement with some previous studies.