Acetylcholine relaxation of renal artery and nitric oxide synthase activity of renal cortex increase with fetal and postnatal age

Abstract

Endothelium-derived nitric oxide (NO) regulates hemodynamics in the fetal kidney and modulates renal perfusion during postnatal maturation. We hypothesize that NO release by renal arteries increases with fetal maturation and contributes to the increased renal perfusion before and after birth. We tested the effect of maturation on relaxation to acetylcholine (ACh; 10-9 M to 10-5 M), the prototypic endothelium-dependent relaxing agent, and sodium nitroprusside (10-9 M to 10-5 M), an NO donor, on isolated main renal arteries obtained from anesthetized fetal guinea pigs of varying gestational age (0.5-0.8, 0.8-0.9, and 0.9-0.97 gestation), and neonatal (1-50 d) and reproductively mature adult guinea pigs. The effect of NO synthase inhibition by nitro-L-arginine (LNA; 10-4 M) and cyclooxygenase inhibition by indomethacin (10-5 M) on ACh relaxation was also measured. Ca2+-dependent NO synthase activity was measured in fetal (0.5-0.87 gestation), neonatal (1- 10 d), and adult (mature) renal cortex by the conversion of [t-14C]arginine to [L-14C]citrulline and the time course compared with the relaxation responses. Sensitivity and maximal relaxation to ACh increased with fetal age. In neonatal renal arteries, maximal relaxation but not sensitivity to ACh increased relative to the fetal arteries. In adult renal arteries, both sensitivity and maximal relaxation increased compared with fetal arteries. Sensitivity but not maximal responses to sodium nitroprusside increased with age but exhibited a different maturational pattern than ACh relaxation. LNA inhibited ACE relaxation in arteries of all ages. Indomethacin reduced the sensitivity to ACh only in the fetal arteries. Ca2+-dependent NO synthase activity of the renal cortex increased during fetal development reaching levels at near term similar to those found in both the newborn and adult kidneys. These results suggest that endothelium-derived NO release by the renal artery and constitutive NO synthase activity in the renal microvasculature increases with fetal and postnatal maturation. Further, the sensitivity of vascular smooth muscle to NO also increases after birth. Thus, functional adaptations in both the endothelium and the vascular smooth muscle contribute to the maturational changes in mechanisms regulating renal hemodynamics before and after birth.