Effects of SIN-1 on peripheral hemodynamics and viscoelastic properties of aorta in anesthetized rabbits

Abstract

In closed-chest, non-barbiturate-anesthetized rabbits, we have used a computer-based parameter estimation method to evaluate the effects of a slow intravenous infusion of SIN-1 (15 micrograms/kg/min for 20 minutes) upon hemodynamic, geometric, viscoelastic, and energetic characteristics of the hindlimb arterial bed from the measurement of abdominal aortic diameter, blood flow, and blood pressure. To evaluate intrinsic effects of SIN-1 upon arterial wall characteristics, a moderate arterial bleeding (3 ml/kg) was performed to achieve a -10% lowering of arterial pressure, i.e., to reach an equivalent blood pressure reference threshold in the absence of the drug. The SIN-1 IV infusion induced a marked blood pressure lowering (-10.0 +/- 2.1%), resulting from a relaxing action on smooth muscle vasculature both in capacitive and resistive components of the hindlimb vascular tree, thereby eliciting a lowering in peripheral resistance (-22.8 +/- 3.1%) and an increased blood flow (+11.7 +/- 3.6%). SIN-1 enhanced vascular compliance (+28.0 +/- 2.2%) and lowered vascular input impedance (-31.2 +/- 8.9%), as confirmed by modulus and phase spectra. SIN-1 IV infusion contrasted bleeding effects by increasing blood flow and maintaining constant or increasing aortic diameter, both of them being lowered by bleeding. The relaxing effect elicited by SIN-1 was further demonstrated by changes in viscoelastic characteristics, and it was further associated with a decreasing energetic demand as well. The present results demonstrated that SIN-1, administered as a slow IV infusion, exhibits vasodilating properties by acting both on capacitive and resistive vessels of the systemic circulation.