Ontogeny of Renal β-Adrenoceptor-Mediated Vasodilation in Sheep: Comparison between Endogenous Catecholamines

Abstract

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P-adrenoceptor mediated vasodilator response to renal nerve stimulation (8) and to intrarenal infusions of epinephrine (unpublished observations) in fetal compared to newborn and adult sheep.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...

Effects of Epinephrine on the Renal Vascular Bed of Fetal, Newborn, and Adult Sheep

“…This response could be inhibited by ICI 1 1835 1, a specific P2-adrenoceptor antagonist (23), supporting the concept that vascular P2-adrenoceptors are functional early during renal maturation. These results are consistent with our previous study demonstrating enhanced renal P-adrenergic response to renal nerve stimulation (24) and infused norepinephrine (9) in fetal sheep and provide evidence of an age-dependent P-adrenergic renal vasodilator mechanism during development in sheep. Furthermore, one may speculate that the ontogeny of renal vascular P-adrenoceptor-mediated responses are similar whether adrenoceptor stimulation occurs with neurotransmitter release or by activation of extrajunctional adrenoceptors via circulating catecholamines (25).…”

“…Comparisons of dose response curves between fetal, newborn, and adult sheep were performed by simultaneous analysis of physiological dose-response curves as described by DeLean et al (17) and previously used by us (8,9). These comparisons were done by using the ALLFIT program adapted for an Apple computer by Martin H. Teicher, Department of Psychiatry, Harvard Medical School.…”

“…A Doppler flow probe, constructed in our laboratory, was secured around the renal artery with care being taken to not interfere with renal innervation. Thereafter, a nonobstructive renal artery catheter was implanted using the method described by Herd and Barger (7) and previously used by us (8,9).…”

Renal Hemodynamic Response to Atrial Natriuretic Factor in Fetal and Newborn Sheep

“…In that regard, these results differ from previous studies (27)(28)(29) demonstrating that the renal vasodilatory response to Padrenoceptor stimulation is greater in fetal sheep than in newborn lambs. A recent study (30) using forskolin, a drug known to activate adenylate cyclase directly (3 I), has suggested that the greater P-adrenoceptor-mediated renal vasodilation in fetal sheep may be at the receptor-hormone level.…”

Cerebral and peripheral circulatory responses to intracranial hypertension in fetal sheep.

“…At high ICP /J-adrenergic blockade in dogs unmasks a large a-adrenergic vasoconstriction, 910 the pattern of which closely resembles that in fetal lambs. However, a recent study showing that /3-adrenergic vasodilation in the kidney is welldeveloped in near-term fetal sheep 22 makes underdevelopment of /3-adrenoceptors an unlikely explanation.…”