The hemodynamic effects of prostacyclin infusions in normotensive and ACTH induced hypertensive conscious sheep

The aim of this study was to determine the effect of ACTH-induced hypertension on the hemodynamic dose-response curves to intravenous infusion of prostacyclin (PGI2) in conscious sheep. PGI2 was infused for 10 minutes at doses of 0.05-0.50 micrograms/kg per min and hemodynamic dose-response curves were performed before, during and after ACTH-induced hypertension. Prior to ACTH administration prostacyclin infusions produced dose dependent decreases in mean arterial pressure (MAP), calculated total peripheral resistance (CTPR) and stroke volume (SV). These changes were accompanied by an increase in cardiac rate (CR) and cardiac output (CO). After five days of ACTH treatment MAP had risen from 72 +/- 1 to 91 +/- 2 mm Hg and infusions of PGI2 produced similar effects on MAP to those seen prior to ACTH. However the effects on CTPR, CO, SV and CR were all potentiated relative to normotensive animals. Three days after ACTH administration had ceased and basal pressure had returned to normotensive levels, the responses of CR, CO and SV to PGI2 infusions were similar to those seen prior to ACTH. However the exaggerated fall in CTPR seen during ACTH treatment was still present and this resulted in a very large decrease in MAP. These studies suggest that in this model of steroid-induced hypertension the resistance vessels are more sensitive to PGI2 and that the blood pressure response to PGI2 is regulated by different mechanisms to those seen prior to ACTH.