A direct growth effect of growth hormone in rat hindlimb shown by arterial infusion

We have developed a method for infusing substances into one hindlimb of the rat via the arterial supply. A catheter attached to an osmotic minipump is inserted into the right superior vesical artery and advanced to the junction of the right common iliac artery. This arrangement permits either constant or pulsatile infusion for 7 days. We employed this method to study the direct action of rat growth hormone (rGH) on the proximal tibial epiphysial plate in hypophysectomized rats. Infusion of neither the solvent nor ovine prolactin (2 micrograms X rat-1 X day -1) affected epiphysial plate width compared with control (uninfused) legs. The rGH infused at 0.4 and 2.0 micrograms X rat-1 X day-1 produced dose-related local growth effects that were of similar magnitude with either constant or pulsatile (eight 1-h pulses/day) infusion. However, the higher dose of rGH also resulted in a systemic effect (i.e., epiphysial plate growth in the uninfused limb), and the pulsatile mode produced a greater systemic effect than that produced by constant infusion. Our results indicate that GH can act directly on cartilage in vivo to maintain growth and that its effectiveness is not enhanced by pulsatile delivery. In contrast, the indirect (i.e., systemic) growth effects of the hormone may be enhanced by intermittent infusion. Our infusion system is well suited for studying the direct effect of substances on hindlimb tissues in conscious, unrestrained rats over extended periods.