Effect of ITF 296 on Total Effective Vascular Compliance in the Anesthetized Dog Under Autonomic Blockade

Abstract

The effects of ITF 296 on venous tone, estimated as changes in total effective vascular compliance (TEVC), were investigated in the anesthetized, spontaneously breathing dog under autonomic blockade. TEVC was calculated from the correlation between the observed changes in central venous pressure (CVP) and the experimentally induced changes in blood volume during an 11-min cycle of whole blood infusion (2 ml/kg/min), withdrawal, and reinfusion. Stepwise increasing doses (short steady-state infusions) of ITF 296 (3, 10, and 30 micrograms/kg/min) resulted in a dose-dependent increase in TEVC (+27, +54, and +67%), whereas mean blood pressure (MBP) was reduced (-12, -23, and -33%, respectively). SIN-1 (10 micrograms/kg/min), administered at the end of the experiment as the reference NO-releasing compound, induced a rather complete venodilation (TEVC +182%) and a marked reduction in MBP (-47%). When nitroglycerin (NTG) was used as the reference compound at 1.5 micrograms/kg/min, a 67% increase in TEVC was observed. These results suggest that ITF 296 exerts a venodilator action but that this effect, and therefore the reduction in venous return, is less than that in response to nitrovasodilators such as SIN-1 or NTG. Furthermore, the vasodilator spectrum of ITF 296 compared to other nitrovasodilators is shifted somewhat more toward the arteriolar bed, with less pronounced venodilator effects, as indicated by the fall in MBP.