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DIRECT CYCLIC AMP (cAMP) STIMULATION OF RENAL VASODILATION IS GREATER IN FETAL (F) COMPARED TO NEWBORN AND ADULT (A) SHEEP

We have previously demonstrated increased β-adrenoceptor mediated renal vasodilation in F compared to N and A sheep. The intra-cellular mechanism mediating this age-dependent β-adrenergic difference was studied by infusing forskolin, a direct stimulator of adenyl cyclase that bypasses the hormone-receptor interactions, into the renal artery of chronically instrumented F (129-139 days gestation; term 145 days), N (7-14 days), and A sheep to test concentration-dependent vasodilation. % changes (%A) in RBF velocity were measured by doppler flowmeter. Estimated concentration (M) of forskolin in renal blood ranged from 4 × 10−7 to 4 × 10−6 M, 3 × 10−7 to 5 × 10−6 M, and 2 × 10−7 to 3 × 10−6 M, in F, N and A, respectively. %A RBF ranged from 21±4 to 47±6 in F (n=5), 9±1 to 39±4 in N (n=5) and 11±2 to 36±3 in A (n=5), respectively. No difference was found between N and A (p=0.21). However, renal vasodilation was significantly greater in F compared to N and A (p=0.004), with a potency ratio F:N and F:A of 3:1. Results demonstrate: 1) an age-dependent cAMP mediated renal vasodilator mechanism; 2) that forskolin produces increased renal vasodilation in F compared to N and A; and 3) that differences in intra-cellular mechanisms may account in part for changes in renal β-adrenergic responses during development.