colforsin-daropate and Hypoxia

PDEIII inhibitors and colforsin daropate hydrochloride (CDH) exert positive inotropic and vasodilatory effects by increasing intracellular cAMP The effect of olprinone (OLP), milrinone (MIL) and CDH on hypoxic pulmonary vasoconstriction (HPV) was evaluated using isolated blood-perfused lung preparations from the rabbit in situ.. We prepared a rabbit constant-flow lung-perfusion model in which HPV was induced by decreasing the FI(O2) from 21% to 3%. We conducted 2 sets of experiments by administering different doses of OLP MIL or CDH into the reservoir. In experiment 1, we administered OLP: 0.02, 0.2, 2, 20, 200 (microg), MIL: 0.1, 1, 10, 100, 1000, or CDH: 0.01, 0.1, 1, 10, 100 (microg). In experiment 2, we administered OLP 2microg or CDH 1 microg after premedication with thapsigargin (TH) 0.1 microM. Following drug administration, changes in pulmonary artery perfusion pressure were measured.. Experiment 1:HPV was inhibited by the administration of 200 microg OLP 100 and 1000 microg MIL, and 10 and 100 microg CDH. Experiment 2:HPV was inhibited by pretreatment with TH, although supplementation with 2 microg OLP or 1 microg CDH did not change the level of inhibition of HPV.. These results suggest that PDEIII inhibitors and CDH inhibit HPV only at high concentrations, the mechanism of inhibition being a decrease in the sensitivity of vascular smooth muscle to Ca2+.

Topics: Animals; Colforsin; Hypoxia; Imidazoles; In Vitro Techniques; Male; Milrinone; Phosphodiesterase Inhibitors; Pulmonary Circulation; Pyridones; Rabbits; Vasoconstriction