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.
SUMMARY. Chronically catheterized lambs (4-37 days postnatal age) (n =35) were studied to test the hypothesis that the products of angiotensin-converting enzyme activity are involved in renal and adrenal responses to normocapnic hypoxemia in immature lambs. Arterial angiotensin II (from 111.0 ± 38.8 to 71.0 ± 38.8 pg/ml, P < 0.01) and aldosterone (from 128.0 ± 98.0 to 62.1 ± 27.9 pg/ml, P < 0.01) concentrations were significantly decreased and vasopressor responses to angiotensin I were greater than 90% inhibited by continuous intravenous infusion of angiotensin-converting enzyme inhibitor (captopril, 2.5 /ig/kg/min, n =16). Baseline mean arterial pressure (64 ± 14 vs. 78 ± 9 mmHg) and urinary sodium excretion rate (UN 8 V 3.04 ± 2.83 vs. 15.00 ± 20.00 fiEq//min) were significantly (P < 0.05) decreased in captopril-treated lambs vs. control lambs. Baseline arterial plasma renin activity was significantly (P < 0.01) increased in captopril-treated vs. control lambs (8.6 ± 9.0 vs. 100.0 ± 64.0 ng/ml per hr). Normocapnic hypoxemia (P02 38 ± 6 torr for 30 minutes) during captopril infusion was associated with no significant (P > 0.05) changes in renal hemodynamics and function, including glomerular filtration rate (from 0.34 ± 0.24 to 0.35 ± 0.25 ml/min per g). Urinary prostaglandin E excretion rate (from 0.655 ± 0.703 to 1.310 ± 1.020 ng/min) and adrenal blood flow (from 2.67 ± 1.69 to 6.24 ± 3.73 ml/min per g) increased significantly (P < 0.05) under these conditions. Arterial epinephrine (from 0.11 ± 0.07 to 1.1 ± 1.8 ng/ml), norepinephrine (0.48 ± 0.38 to 3.2 ± 5.4 ng/ml), and arginine vasopressin (from 5.11 ± 2.20 to 10.70 ± 8.61 jiU/ml) also increased significantly (P < 0.05) in response to hypoxemia during angiotensin-converting enzyme inhibition with captopril. None of these responses to hypoxemia were significantly different from that of uninhibited (control) lambs (n=19). In contrast, cortisol response to hypoxemia was significantly (P < 0.05) less in captopril-treated lambs (captopril vs. control, -1.00 ± 1.90 vs. 3.40 ± 3.30 /ig/dl). These data suggest that the products of angiotensin-converting enzyme activity are not important regulators of renal responses to hypoxemia, but may be involved in cortisol responses to normocapnic hypoxemia in immature lambs. (Circ Res 52: 179-187, 1983)
ABSTRACT. The present study was designed to investigate the effect of acute (2 h) and chronic aldosterone (4 days) infusion on urinary kallikrein excretion rate and on renal handling of Na+ and K+ in chronically catheterized fetal lambs e l 1 5 days gestation (n = 6) and >I25 days gestation (n = 7). Chronic aldosterone infusion decreased plasma renin activity in both groups of fetuses. Both acute and chronic aldosterone infusion produced significant decreases in UNa + V in fetuses >I25 days and in the majority of fetuses e l 1 5 days gestation (five of six). Aldosterone infusion did not increase K+ excretion in either group of fetuses. It is also demonstrated that chronic aldosterone infusion induced an increase in urinary kallikrein excretion rate in both groups of fetuses. Taken together, these results demonstrate that aldosterone has antinatriuretic but no kaliuretic effects during fetal life, but produces a rise in urinary kallikrein excretion rate during the last trimester of gestation in fetal lambs. (Pediatr Res 19: 1048-1052,1985 Abbreviations UKall, urinary kallikrein PRA, plasma renin activity HUK, human urinary kallikrein 'H-TAME, N-(p-tosy1)-1-arginine-PHI-methyl ester-hydrochlorideAldosterone acts on the kidney to increase sodium reabsorption in exchange for either potassium or hydrogen ion (I) and to stimulate renal kallikrein production (2). However, the role of aldosterone on the fetal renal function is not well defined. In respect to sodium metabolism, it has been shown that the percentage of filtered sodium excreted is elevated during fetal life (3,4) and in premature infants (5) suggesting a partial unresponsiveness of the distal nephron to aldosterone.On the other hand, it has been demonstrated that UKall excretion rate increases significantly during the last trimester of gestation in fetal lambs (6). Since this rise correlated with an increase in plasma aldosterone concentration, it was suggested that aldosterone may be an important modulator of renal kallikrein production during renal maturation (6).The present study was designed to explore in detail the effect of acute and chronic administration of aldosterone on UKall excretion rate during the last trimester of gestation in chronically Received April 5, 1985; accepted June 4, 1985 catheterized fetal lambs. Moreover, the quantitative relationship between plasma levels of aldosterone and renal handling of sodium and potassium was also evaluated. METHODSAnimal preparation and surgical procedures. The fetuses of 13 pregnant sheep of Dorset and Suffolk mixed breeding were studied. Six fetuses were between 99 and 107 days gestation (group I) and seven fetuses were between 125 and 13 1 days gestation (group 11) (term was 145 days) at the time of surgery. Gestational ages were based on the induced ovulation technique as described previously (7).Prior to surgery, the animals were fasted for 48 h. Anesthesia of the ewe and surgery of the fetus were performed as described previously (8). Briefly, the pregnant ewe was anesthetized using a mixture of...
The present study was designed to determine the influence of renal nerves in mediating the renal response to volume expansion in conscious newborn lambs. Bilateral renal denervation (n = 9) or sham surgery (n = 14) was carried out in newborn lambs 3 to 4 days before performing experiments. Lambs were between 6 and 12 days of age when studied. Chronic denervation did not alter basal neonatal renal function nor renal hemodynamics. Volume expansion with isotonic saline equal to 5% of body weight was associated with a fall in hematocrit and an increase in mean arterial blood pressure, glomerular filtration rate, urine flow rate, and Na+ excretion in intact and denervated lambs. In intact lambs, atrial natriuretic factor increased from 98 +/- 28 to 176 +/- 48 ng/ml during volume expansion and remained elevated for 1 h after volume expansion. In addition, plasma renin activity fell from 21 +/- 5 to 8 +/- 1 ng.ml-1.h-1 and aldosterone levels fell from 160 +/- 24 to 59 +/- 7 pg/ml by 150 min after the start of volume expansion. Similar changes in atrial natriuretic factor, plasma renin activity, and aldosterone were observed in denervated lambs. However, the increase in glomerular filtration rate, Na+ excretion, and fractional excretion of Na+ after volume expansion were significantly less in denervated than in intact lambs. Thus, in the newborn, the renal nerves do not appear to play a role in influencing basal renal hemodynamics and renal function but, as in the adult, the renal sympathetic nervous system does play a role in regulating fluid and electrolyte excretion during hypervolemia.
Previous work in our laboratory has demonstrated impairment of cardiopulmonary reflex control of renal sympathetic nerve activity (RSNA) during the newborn period. The present study was designed to test the hypothesis that this delayed maturation is secondary to incomplete central integration of vagal afferent input. Term fetal (135-140 days; n = 6), newborn (3-7 days of age; n = 8), and young adult (6-8 wk old; n = 8) sheep anesthetized with alpha-chloralose underwent vagal afferent nerve stimulation. All animals had undergone prior sinoaortic denervation to eliminate influences from the arterial baroreceptors. After determination of optimal stimulation parameters, RSNA responses to gradual increases in stimulation frequency (1.0-16 Hz) were recorded and compared by one-way ANOVA. RSNA decreased progressively with increased frequency of stimulation in all three groups of animals. When comparing the three groups at any given frequency of stimulation, reflex withdrawal of RSNA tended to be more pronounced in newborn lambs (P < 0.05 for 1 and 4 Hz). Heart rate (HR) was also noted to decrease significantly with vagal afferent stimulation in each of the groups, but no significant differences in the reflex decreases in HR were noted among the three groups of animals. These results demonstrate that central integration of vagal afferent input is intact in fetal and newborn sheep. These results suggest that the delayed maturation of cardiopulmonary reflex-mediated changes in RSNA seen early in development appears to depend on intrinsic alterations in baroreceptor function rather than incomplete central integration.
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