RESINIFERATOXIN AND PIPERINE - CAPSAICIN-LIKE STIMULATORS OF OXYGEN-UPTAKE IN THE PERFUSED RAT HINDLIMB

The naturally occurring capsaicin-like molecules, resiniferatoxin (RTX , Euphorbia spp.) and piperine (Piper nigrum), each stimulated oxygen uptake (VO2) in association with increased vascular resistance in a co ncentration-dependent manner when infused into the perfused rat hindli mb. 5 mu M glyceryl trinitrate (GTN, a nitrovasodilator) significantly blocked the oxygen and pressure responses to both RTX and piperine, i ndicating a close relationship between changes in VO2, and the vasocon striction. Concentrations greater than those required for maximal VO2 resulted in an inhibition of VO2, although perfusion pressure continue d to increase. Time course studies showed that both RTX and piperine a t high doses resulted in a tri-phasic response. An initial phase of tr ansient VO2 stimulation was followed by a second phase of inhibition. A third phase involving an often larger but transient stimulation of V O2 followed removal of the agents and continued after the pressure ret urned to basal. The actions of RTX and piperine were similar to those of other active capsaicin-like molecules tested previously in this sys tem, including capsaicinoids (Capsicum spp.), gingerols (Zingiber offi cinale), and shogaols (Zingiber officinale). RTX was the most potent, and piperine the least potent of this series. Although receptor involv ement has yet to be unequivocally established, the data are consistent with the presence of a functional capsaicin-like (vanilloid) receptor in the vasculature of the rat hindlimb that mediates vasoconstriction and oxygen uptake. These findings may have implications for the futur e development of thermogenic agents.