ABSTRACT. The renal hemodynamic response to renal arterial infusions of norepinephrine was compared to epinephrine infusions during renal a-adrenoceptor blockade in chronically instrumented and unanesthetized fetal (127-141 days gestation; term 145 days), newborn (6-10 days old), and nonpregnant adult sheep. Infusions of either catecholamines produced renal vasodilation which was of greater magnitude in fetal compared to newborn and adult sheep. Maximal increases in renal blood flow velocity during norepinephrine infusion were 64 f 5% in fetal, 23 f 4% in newborn, and 24 f 7% in adult sheep ( p < 0.001). Extremely high catecholamine levels are observed during fetal stress (1) and during birth (2,3), with the predominant circulating catecholamine being norepinephrine. In contrast, the sympathoadrenal response to stress in adults is associated with significantly lower plasma catecholamine values where epinephrine is the major circulating catecholamine (4). Because the sympathoadrenal system plays an important role in modulating renal hemodynamics ( 3 , knowledge about differences in sympathoadrenal activity during development and its functional role in determining RBF is of interest in perinatal medicine. Little is known about the ontogeny of sympathoadrenal stimulated renal vasodilation. Buckley et al. (6,7) have examined the postnatal development of renal vasodilatory mechanisms in anesthetized piglets (6, 7). Their studies have shown that the Padrenergic vasodilatory mechanism in the renal vascular bed of swine is absent at birth and appears postnatally at 2 wk. However, in chronically instrumented sheep, we have demonstrated during a-adrenoceptor blockade, enhanced renal P-adrenoceptor mediated vasodilator response to renal nerve stimulation (8) and to intrarenal infusions of epinephrine (unpublished observations) in fetal compared to newborn and adult sheep. In contrast, these results differ from dopamine-mediated vasodilator responses which are of considerably smaller magnitude in fetal, newborn, and adult sheep (9).Since levels of plasma catecholamines and of norepinephrine, the predominant circulating catecholamine found during stress, are age dependent, and because norepinephrine and epinephrine differ in their ability to stimulate the vascular P-adrenergic receptor (lo), the present protocol was designed to compare the renal hemodynamic response to renal arterial norepinephrine and epinephrine infusions during renal a-adrenoceptor blockade in chronically instrumented fetal, newborn, and adult sheep. METHODSAnimal preparation and surgical procedures. Fetuses of seven pregnant sheep of Dorset and Suffolk mixed breeding were studied between 127 and 141 days gestation (term was 145 days). Gestational ages were based on the induced ovulation technique as previously described (I 1).Ewes were fasted for 48 h prior to surgery. General anesthesia of the ewe and fetal surgery were performed as previously described (1 1). Briefly, when the ewe was receiving a mixture of 1% halothane. 33% oxvgen. and 66% nitrous oxi...

ABSTRACT. The renal hemodynamic response to renal artery infusions of epinephrine were compared in conscious and chronically instrumented fetal (125-139 days gestation; term 145 days), newborn (5-13 days postnatal), and nonpregnant adult sheep. Epinephrine produced similar dose related decreases in renal blood flow velocity in all three groups. The mean estimated concentration of epinephrine in renal blood producing a 50% decrease in renal blood flow velocity, ED50, was 0.008 pglml. Epinephrine infusions during renal a-adrenoceptor blockade with phentolamine produced increases in renal blood flow velocity that were of greater magnitude in fetal compared to newborn and adult sheep. The maximal increase in renal blood flow velocity observed were 57 f 11%, 22 & 3%, and 18 + 3% in fetal, newborn, and adult sheep, respectively (p < 0.001). This vasodilation produced by epinephrine during a-adrenoceptor blockade was completely inhibited by ICI 118,551, a P2-adrenoceptor antagonist. Inhibition of renal vascular @-adrenoceptors with propranolol in fetal sheep did not enhance a-adrenoceptor-mediated renal vasoconstriction with epinephrine infusions. Results of the present study demonstrate similar renal vasoconstrictor responses to renal artery infusion of epinephrine in fetal, newborn, and adult sheep. In contrast, the renal vasodilator responses observed with epinephrine infusions during renal a-adrenoceptor blockade were greater in fetal compared to newborn and adult sheep. However, epinephrine-mediated renal vasoconstriction was not enhanced by blockade of Padrenoceptors in fetal sheep. (Pediatr Res 23: 181-186, 1988 than 10-fold higher than in resting adults (1). However, despite these high levels, the phenomenon of birth is associated with an increase in RBF and glomerular filtration (2) suggesting that the developing kidney may respond differently to catecholamine stimulation than the adult.In this respect, Buckley et al. (3) found that the renal vasculature of anesthetized newborn piglets is less sensitive to aadrenoceptor stimulation than older swine. However, Jose et al. (4) have shown that anesthetized puppies were more sensitive to intrarenal epinephrine than adults and had increased renal aadrenoceptor affinity and density compared to adult dogs (5).To further investigate the functional role of circulating catecholamines in modulating renal hemodynamics during devel-A opment, the present study was designed to specifically examine the developmental response of the renal vascular bed to direct intrarenal infusions of epinephrine, using conscious and chronically instrumented fetal, newborn, and nonpregnant adult sheep. METHODSAnimal preparation and surgical procedures. Fetuses of 14 pregnant sheep of Dorset and Suffolk mixed breeding were studied between 125 and 139 days gestation (term 145 days). Gestational ages were based on the induced ovulation technique as previously described (6).Ewes were fasted for 48 h before surgery. General anesthesia of the ewe and fetal surgery were performed as previously descri...

ABSTRACT. Postjunctional a]-and a2-adrenoceptor vasoconstrictor responses were evaluated in isolated segments of main renal artery, segmental renal artery, and renal vein from fetal (130-138 d of gestation; term 145 d), newborn (3-15 d age), and nonpregnant adult sheep. Vascular rings were mounted a t their optimal resting tension and responses to phenylephrine (aI-adrenoceptor agonist) and guanabenz and UK14304 (both az-adrenoceptor agonists) were determined. Optimal resting tension increases with development in the main renal artery, segmental renal artery, and renal vein of sheep. Arterial vessels develop more isometric tension to al-adrenoceptor stimulation than to a2-adrenoceptor stimulation, whereas venous segments develop similar isometric tension to al-and az-adrenoceptor stimulation. The segmental renal artery develops more isometric tension to a2-adrenoceptor stimulation than the main renal artery. No large developmental differences exist among vessels in the sensitivity (concentration required for half maximal response, EDs0) to a-adrenoceptor stimulation except for the renal vein with a2-adrenoceptor stimulation. Maximum isometric tension corrected for vessel cross-sectional area decreases with age for all vessels with both a,-and a2-adrenoceptor stimulation. These findings may reflect developmental differences in receptor number and affinity or differences in vascular smooth muscle function. In addition, these data suggest that whereas both aland a2-adrenoceptors mediate vasoconstriction in the renal circulation, they may do so at different sites. (Pediatr Res 25:461-465, 1989 46Recent studies in this laboratory have demonstrated that renal vascular a l -and az-adrenoceptors are functional and can produce renal vasoconstriction in fetal sheep and newborn lambs (I). Moreover, the renal hemodynamic response to a l -and a2-adrenoceptor stimulation changes during maturation with fetal and newborn a?-adrenoceptor responses less than those observed in adult sheep, whereas the 0,-adrenoceptor responses were similar (1).Contrary to our results (I), recent studies by Tayo et ul. (2) using isolated vascular rings demonstrated that the a2-adrenoceptor-mediated contractile response is greater in 4-to 8-wk-old rabbits than in adult animals, suggesting that there may be a loss of a2-adrenoceptor-mediated contraction with maturation. Differences between the study by Tayo et a/. (2) and our previous results (1) are difficult to explain. However, some of the differences between the two studies may be due to comparing in vivo experiments, where the overall hemodynamic response is studied. with in vitro experiments, where specific vascular segments arc studied.Therefore, the present study was designed to examine possible regional developmental differences in a , -and a?-adrenoceptor-, mediated vasoconstrictor responses in the developing renal vas-. cular bed. Isolated segments of MRA, SRA, and RV from fetal. newborn, and nonpregnant adult sheep were studied. MATERIALS A N D METHODSAnirnu1.r. Vessels from seven fetal...