Reversal of cadmium-induced hypertension by D-myo-inositol-1,2,6-trisphosphate

The aim of this experiment was to test whether a chelating agent, D-myo-inositol-1,2,6-trisphosphate (PP56), could reverse cadmium-induced hypertension. Four groups of weanling female Long-Evans rats received ad libitum a rye-based, metal-poor diet and deionized water fortified with essential metals for 15 mo from the time of weaning. A control group received neither cadmium nor chelating agent. A second group had 0.1 ppm cadmium added to their water from weaning through mo 5. A third group had 60 ppm PP56 added to their water for mo 6-10. The fourth group had 0.1 ppm cadmium added to their water from weaning through mo 5 and 60 ppm PP56 from mo 6-10. All groups were followed without either cadmium or PP56 for mo 11-15. At approximately monthly intervals, systolic pressure was measured by the indirect tail cuff method in unanesthetized rats. Chronic cadmium feeding induced the expected hypertension, with an average increase in systolic pressure of about 15 mm Hg; the pressor effect persisted with little change for the 10 mo after cadmium was withdrawn. PP56 completely reversed the cadmium-induced hypertension, and the inhibition persisted for 5 mo after PP56 was withdrawn. PP56 by itself had no demonstrable depressor effect.