Ontogeny of renal hemodynamic response to renal nerve stimulation in sheep

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Abstract
The renal hemodynamic response to direct electrical stimulation of renal nerves was studied in conscious and chronically instrumented fetal (130-142 days gestation; term 145 days), newborn (7-12 days postnatal), and adult nonpregnant sheep. Renal nerve stimulation (RNS) produced a significant decrease in renal blood flow (RBF) velocity and a significant increase in renal vascular resistance (RVR) in all three groups of animals. The overall decline in RBF velocity and the overall rise in RVR was less pronounced in fetal than in adult sheep (P less than 0.05). Changes in RBF velocity and RVR using an RNS frequency of 16 Hz were -35 +/- 4 and 81 +/- 19% in fetal sheep, -61 +/- 10 and 374 +/- 128% in newborn lambs, and -84 +/- 12 and 540 +/- 94% in adult sheep, respectively. RNS during intrarenal infusion of the alpha-adrenoceptor antagonist phentolamine was associated with a significant increase in RBF velocity and decrease in RVR in both fetal sheep and newborn lambs, but not in adult sheep. Moreover, it was found that the rise in RBF velocity and the decrease in RVR associated with RNS during alpha-adrenoceptor antagonism were completely inhibited by intrarenal infusion of ICI 118,551, a beta 2-adrenoceptor antagonist and unaffected by either cholinergic or dopaminergic antagonists. Taken together, these results suggest that the overall renal vasoconstrictor response to RNS is age dependent. Furthermore, the present results demonstrate that, contrary to observations made in adult animals, RNS can produce renal vasodilation in immature animals that is mediated by beta 2-adrenoceptors.