Biomedical subjects

J E Robillard

Publications and source records attributed to J E Robillard.

At least 55 records · Page 3Linked to original sources

PubMed1993

Developmental regulation of the alpha 1B-adrenoceptor in the sheep kidney.

The expression of renal alpha 1B-adrenoceptor (alpha 1B-AR) mRNA was studied and contrasted with the expression of renal renin mRNA in fetal and newborn sheep. Fetal sheep between 90 and 91, 116 and 118, and 139 and 141 d gestation (term is 145 d gestation) as well as newborn lambs between 1 and 2 d old and 8 and 10 d old were studied (n = 3 for each age range). The role of the renal nerves in regulating changes in alpha 1B-AR gene expression was also investigated by measuring renal cortical alpha 1B-AR mRNA levels and receptor kd and maximum number of binding sites in 24-h-old lambs that were either denervated (n = 6) or sham-operated (n = 5) 3 d before birth. During development, renal alpha 1B-AR mRNA levels show a marked increase in term fetuses; this increase persists into the first 2 d of life and is distinct from the developmental pattern seen for renal renin mRNA levels. Denervation of term fetuses does not alter the expression of renal alpha 1B-AR mRNA in newborn lambs when compared with sham-operated controls but decreases significantly the expression of the renin gene (p < 0.05). These results suggest that the alpha 1B-AR gene is developmentally regulated in the kidney in a pattern distinct from that seen for renin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Mechanisms regulating renal sodium excretion during development.

The present review focuses on the ontogeny of mechanisms involved in renal sodium excretion during renal maturation. The effect of birth on renal excretion of sodium and the role played by the different tubular segments in the regulation of sodium excretion during maturation are discussed. The influence of circulating catecholamines and renal sympathetic innervation in regulating sodium excretion during renal development is reviewed. The effects of aldosterone, atrial natriuretic factor, and prostaglandins on sodium regulation during renal maturation are discussed. Special emphasis is given to the potential role of glucocorticoids in modulating sodium excretion early in life.

Aldosterone↗

PubMed1992

Addition of metolazone to overcome tolerance to furosemide in infants with bronchopulmonary dysplasia.

A decreased response to the loop diuretic furosemide develops within a few doses in young infants. We tested the hypothesis that the use of the thiazide-like diuretic metolazone, in combination with furosemide, would inhibit water and electrolyte reabsorption and overcome pharmacologic tolerance to furosemide alone. Infants with bronchopulmonary dysplasia of similar gestational and postnatal ages were randomly assigned to one of three groups. Group 1 (n = 6) received furosemide (1 mg/kg per dose) intravenously every 24 hours for a total of five doses. Group 2 (n = 8) received the same treatment as group 1, but in addition metolazone (0.2 mg/kg per dose) was given enterally with doses 3 and 4 of furosemide. Group 3 (n = 8) received metolazone (0.2 mg/kg per dose) enterally every 24 hours for five doses. Urine was collected before the first diuretic dose and throughout the study for determination of the urine flow rate; urinary excretion of sodium, chloride, and potassium; and creatinine clearance. Urinary flow rate and urinary sodium and chloride excretion increased after the first dose in all groups. In the infants treated with either furosemide or metolazone, urinary flow rate and urinary and chloride excretion returned to baseline values after the last three doses. In contrast, when furosemide was administered with metolazone, urinary flow rate and urinary excretion of sodium, chloride, and potassium were greater than the values for baseline and for the previous dose, as well as for the corresponding doses of furosemide in group 1 and metolazone in group 3. Tolerance to furosemide (group 1) and metolazone (group 3) appeared to be explained by compensatory increased sodium and chloride reabsorption without changes in creatinine clearance. We conclude that the administration of metolazone with furosemide enhances diuresis, natriuresis, and chloruresis and overcomes the rapid development of tolerance to furosemide in infants with bronchopulmonary dysplasia by blocking the compensatory increase in renal sodium and chloride absorption.

Bronchopulmonary Dysplasia↗

PubMed1992

Ontogeny of baroreflex control of renal sympathetic nerve activity and heart rate.

The purpose of this study was to characterize the developmental changes in baroreflex function during fetal and postnatal life in sheep. Resting mean arterial blood pressure increased significantly from 55 +/- 2 mmHg in fetuses to 86 +/- 3 mmHg in newborn lambs and to 105 +/- 4 mmHg in 4- to 6-wk-old lambs. The sensitivity (gain) of the renal sympathetic nerve activity (RSNA) response to baroreceptor stimulation was greater (P < 0.05) in fetuses (-7.7 +/- 1.9%/mmHg) than in newborn (-2.9 +/- 0.1%/mmHg) and 4- to 6-wk-old lambs (-2.2 +/- 0.2%/mmHg). The threshold and saturation pressures for the baroreflex function curve were lower (P < 0.05) in fetuses (44 +/- 2 and 61 +/- 2 mmHg) than in newborn (59 +/- 4 and 106 +/- 5 mmHg) or 4- to 6-wk-old lambs (78 +/- 5 and 132 +/- 6 mmHg). Similar findings were observed when the heart rate response to baroreceptor stimulation was examined. Additional experiments were performed in newborn and 4- to 6-wk-old lambs to determine whether the rise in arterial blood pressure associated with postnatal maturation contributed to baroreflex resetting. Sustained elevation of arterial blood pressure by 15-20 mmHg for over 90 min did not reset the baroreflex function curve in either newborn or 4- to 6-wk-old lambs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Renal nerves modulate kidney renin gene expression during the transition from fetal to newborn life.

The role of renal nerves in regulating changes in plasma renin activity (PRA) and renal renin gene expression was studied in intact (n = 6) and denervated (n = 6) fetal sheep before birth and during the first 24 h after delivery. Renal denervation completely blunted the rise in PRA observed 24 h after delivery in newborn lambs; in lambs with intact kidneys, PRA increased significantly (P less than 0.05) from 3.26 +/- 0.60 (predelivery) to 6.34 +/- 1.85 ng angiotensin I (ANG I).ml-1.h-1 (24 h postdelivery), while in lambs with denervated kidneys, predelivery and post-delivery values were 2.84 +/- 0.19 and 2.49 +/- 0.45 ng ANG I.ml-1.h-1, respectively. Renin mRNA levels were significantly lower (P less than 0.001) in denervated than in intact kidneys 24 h after birth. A close analysis of these results also revealed that renin mRNA levels were significantly higher (P less than 0.001) in intact kidneys of newborn lambs delivered vaginally (n = 3) than in newborn lambs delivered by cesarean section (n = 3). These results suggest that renal nerves play an important role in regulating renin gene expression and PRA during the transition from fetal to newborn life.

Aging↗

PubMed1992

Effects of volume expansion on renal sympathetic nerve activity and cardiovascular and renal function in lambs.

To assess the cardiopulmonary baroreflex in the immature animal, effects of volume expansion on changes in right atrial pressure, renal sympathetic nerve activity, and renal function were measured in chronically instrumented newborn (4-8 days; n = 13) and older lambs (4-5 wk; n = 14). Studies were carried out for 30 min before and 2 h after volume expansion with 6% Dextran 70 (25 ml/kg). Right atrial pressure increased by 4.0 +/- 0.5 mmHg in newborns and by 8.8 +/- 0.6 mmHg in older lambs within 15 min of volume expansion (P less than 0.001). After volume expansion, heart rate decreased in newborns from 237 +/- 6 beats/min to a nadir of 211 +/- 7 beats/min 2 h later (P less than 0.001) but remained constant at control levels of 148 +/- 9 beats/min in older lambs. Maximal inhibition of renal sympathetic nerve activity was achieved at 15 min in older lambs (-50.1 +/- 7.5%) and at 60 min (-58.3 +/- 10.9%) in newborns in which there was a prolonged sympathoinhibition (P less than 0.001). There was also a significant diuretic response in both groups but a limited natriuretic response to volume expansion in newborns (P greater than 0.05) compared with older lambs (P less than 0.001). These data demonstrate the presence of the cardiopulmonary baroreflex in the first week of life in lambs. The sustained sympathoinhibition and bradycardia seen in response to volume expansion in newborns but not in older lambs support the hypothesis that the reflexes controlling arterial pressure and blood volume change with postnatal maturation.

Animals↗

PubMed1992

Ontogeny of DA1 receptor-mediated natriuresis in the rat: in vivo and in vitro correlations.

The natriuretic and diuretic effects of dopamine are attenuated in the young. Because dopamine has actions on receptors (e.g., adrenergic, serotonin) other than dopamine, we studied a novel dopamine agonist, pramipexole, which has a selectivity to both DA1 and DA2-receptor subtypes. Intravenous administration of pramipexole resulted in a dose-related (1, 10, and 100 micrograms.kg-1.min-1) increase in urine flow and absolute and fractional sodium excretion and a decrease in mean arterial pressure (MAP) in three groups of rats studied. Pramipexole induced a greater decrease in MAP in 6- to 7- (n = 5) and 9- to 16- (n = 6) than in 3- to 4-wk-old (n = 8) rats; the natriuresis and diuresis were greatest in 12- to 16- and least in 3- to 4-wk-old rats. The renal effects of pramipexole were mainly due to actions at the DA1 receptor, since these effects were completely blocked by the coinfusion of a DA1 antagonist, SKF 83742. To explore further a cause of the attenuated natriuretic effect of pramipexole in the young, we studied the effect of a selective DA1-receptor agonist, fenoldopam, on amiloride-sensitive 22Na+ uptake in renal brush-border membrane vesicles. The 3-s amiloride-sensitive uptake was inhibited (45%) by fenoldopam (5 x 10(-5)M) in 9- to 16- (n = 6) but not in 3- to 4-wk-old (n = 5) rats. These studies suggest that the attenuated natriuretic effect of dopamine in the young is in part due to decreased DA1 action on the brush-border membrane Na(+)-H+ exchanger.

Aging↗

PubMed1992

Ontogeny of renal response to specific dopamine DA1-receptor stimulation in sheep.

The present study was designed to characterize the developmental changes in the renal responses to dopamine DA1-receptor activation in chronically instrumented preterm (109-115 days) and near-term (130-140 days, full term 145 days) fetal sheep. Cumulative doses of the selective DA1-agonist fenoldopam increased mean arterial blood pressure (MABP) in both preterm (+16 +/- 3%) and near-term fetuses (+16 +/- 3%) but had no significant effect on renal blood flow velocity. Infusion of the DA1-antagonist SCH-23390 did not affect the increase in MABP, suggesting that the effect of fenoldopam on MABP was not directly related to activation of DA1-receptors. Fenoldopam infusion had no significant effects on renal function parameters in preterm fetuses. In near-term fetuses, however, fenoldopam increased urinary flow rate (82.6 +/- 20.9%, P < 0.003), glomerular filtration rate (GFR; 16.6 +/- 4.9%, P < 0.01), urinary sodium excretion (40.1 +/- 14.9%, P < 0.02), and fractional excretion of sodium (26.8 +/- 11.2%, P < 0.03). Infusion of the DA1-antagonist SCH-23390 blocked the fenoldopam-induced diuresis and natriuresis but had no significant effect on the rise in GFR. Fenoldopam infusion had no significant effects on plasma renin activity and plasma aldosterone concentration and on urinary prostaglandin (PG) excretion (PGE2, PGF2 alpha, and 6-keto-PGF1 alpha). Taken together, these results suggest that the renal effect of DA1-receptor activation is age dependent and that stimulation of DA1-receptor in near-term fetuses is associated with a diuresis and natriuresis that seem to be independent of renal hemodynamics and adrenal effects.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1992

Regulation of sodium metabolism and extracellular fluid volume during development.

In addition to regulating developmental changes in body fluid content, the newborn kidney must maintain a positive sodium balance to ensure adequate body growth. Mechanisms by which the developing organism perceives changes in volume and the manner in which the kidney responds to these changes have been reviewed. Perception of changes in ECF volume is sensed by volume receptors that involve central nervous system signal processing (e.g., low- and high-pressure volume receptors) before influencing the kidney by way of the renal nerves or that are directly coupled with the kidney and do not involve central nervous system processing (e.g., juxtaglomerular apparatus, ANF, hepatic factors). Results presently available demonstrate that these mechanisms are functional early in life and that their sensitivity changes during development in accordance with the needs of the organism. In addition, the developing kidney has unique characteristics that allow it to maintain a positive sodium balance necessary for growth.

Adult↗

PubMed1991

Characterization of renal alpha-adrenoceptor subtypes in sheep during development.

Intrarenal arterial infusion of alpha 1-adrenergic agonists decreases renal blood flow, glomerular filtration rate, and water and sodium excretion to a greater extent in fetus and newborn than in adult sheep. In vitro renal vascular effects of alpha 1- and alpha 2-adrenergic agonists are also greater in fetus than newborn or adult. The present studies were designed to examine the ontogeny of renal alpha-adrenoceptor subtypes in sheep for whom the renal effects of alpha-adrenergic agonists have been described at similar postconceptional ages. With the use of radioligand-binding techniques, specific binding of [3H]prazosin (alpha 1-adrenergic antagonist), [3H]idazoxan, and [3H]rauwolscine (alpha 2-adrenergic antagonists) was studied in fetus, lamb, and adult sheep kidneys. The specific binding of the three radioligands was greatest in fetal and least in adult kidneys. Analysis of Scatchard plots revealed a greater renal alpha 1-adrenoceptor density in fetuses than in lamb or adults. Renal alpha 2-adrenoceptor density was also greater in fetuses than in lambs. These studies suggest that the increased renal alpha 1- and alpha 2-adrenergic effects in fetal sheep are related to increased alpha-adrenoceptor density. Competition experiments and rank adrenergic antagonist potency suggested the presence of only the alpha 1b-adrenoceptor in fetal and adult sheep kidneys. The alpha 2-adrenoceptor that was found only in the fetal sheep had a low affinity to rauwolscine, which is unlike that described in most species for alpha 2-adrenoceptors.

Adrenergic alpha-Antagonists↗

PubMed1991

Role of renal sympathetic nerves in lambs during the transition from fetal to newborn life.

To determine the role of renal sympathetic nerves in influencing renal function during the transition from fetal to newborn life, studies were carried out in conscious, chronically instrumented fetal sheep with either bilateral renal denervation (n = 11) or intact renal nerves (n = 12), 3-6 d after surgery. Endocrine, renal, and cardiovascular parameters were measured before and after delivery of lambs by cesarean section. Blood pressure and heart rate were similar in intact and denervated fetuses, and increased after delivery in both groups. There was also a transient diuresis and natriuresis, in the immediate postnatal period, the response being significantly greater in denervated than intact lambs (P less than 0.05). By 24 h postnatally, fluid and electrolyte excretions were similar in both groups, and significantly less than fetal levels. In the absence of renal nerves, the normal rise in plasma renin activity at birth was attenuated. These data provide evidence that renal sympathetic nerves play an important role during the transition from fetal to newborn life, and support the premise that birth is associated with sympathetic activation.

Animals↗

PubMed1991

Negative regulation of angiotensinogen gene expression by glucocorticoids in fetal sheep liver.

The effect of glucocorticoids in regulating liver angiotensinogen gene expression was studied in chronically instrumented fetal sheep during the last trimester of gestation and was compared with the expression of other hepatic genes (prothrombin, factor IX, and albumin). Four sets of twins were studied at 118 d of gestation, and three sets were studied at 138 d of gestation (term, 145 d). One of each set of twins was infused intraperitoneally with cortisol (5 mumol.mL-1.h-1) for 48 h, whereas the other twin received the same volume (1 mL/h) of normal saline. Plasma cortisol concentration increased from 0.32 +/- 0.12 and 2.7 +/- 0.12 nmol/100 mL to 44.2 +/- 20.0 and 37.7 +/- 8.2 nmol/100 mL in 118- and 138-d fetuses, respectively, during the cortisol infusion; no changes were observed in fetuses infused with saline alone. At the end of the infusion period, the animals were anesthetized, the fetal liver was removed, and total cellular RNA was isolated and probed for angiotensinogen, prothrombin, factor IX, and albumin. The results demonstrated that cortisol infusion decreased angiotensinogen mRNA by 61% in 138-d fetuses and albumin mRNA expression by 2.4-fold in 118-d fetuses and by 3.4-fold in 138-d fetuses. On the other hand, cortisol had no effect on fetal factor IX gene expression but increased prothrombin mRNA levels by 65% in 118-d fetuses and 62% in 138-d fetuses. Taken together, our results suggest that, during fetal life, angiotensinogen gene expression is negatively regulated by glucocorticoids. This effect is not universal because cortisol increases fetal prothrombin gene expression.

Angiotensinogen↗

PubMed1991

Endocrine effects of ventilation, oxygenation and cord occlusion in near-term fetal sheep.

The transition from fetal to newborn life is associated with significant endocrine changes. Some of these changes may be triggered by the effects of spontaneous respiration, increased oxygenation and removal of the placental circulation at birth. We, therefore, studied endocrine function during in utero ventilation, oxygenation and cord occlusion, in nine chronically-instrumented fetal sheep aged 137 to 140 days of gestation. During the sequential effects of in utero ventilation and oxygenation, plasma renin activity (PRA) and angiotensin II (AII) remained at control levels of 6.3 +/- 1.9 ng/ml per h and 66 +/- 15 pg/ml. After cord occlusion, PRA increased to 10.3 +/- 2.2 ng/ml per hr and AII increased to 86 +/- 24 pg/ml, the latter being non-significant. Plasma cortisol levels also increased from control levels of 3.5 +/- 1.0 to 6.7 +/- 0.8 g/dl during cord occlusion (P = 0.02). During the sequential effects of ventilation, oxygenation and cord occlusion, plasma epinephrine increased from control levels of 87 +/- 17 to 492 +/- 142 pg/ml (P = 0.04), and plasma norepinephrine levels increased slightly from 620 +/- 112 to 850 +/- 214 pg/ml. These data provide evidence that many of the changes in endocrine function seen at birth result from factors other than spontaneous respiration, oxygenation and umbilical cord occlusion.

Air↗

PubMed1990

Ontogeny of renal beta adrenoceptors in the sheep.

The renal vasodilatory response to beta-2 adrenoceptor stimulation is greater in fetal than adult sheep. Since this phenomenon could not be explained by differences in cAMP-mediated events, we examined the ontogeny of renal beta adrenoceptor subtypes by radioligand binding using the beta adrenergic antagonist 125I-pindolol. The specific binding of 125I-pindolol was saturable, reversible, and stereoselective. Competition studies using the selective beta-1 and beta-2 adrenergic antagonists (ICI 89406 and ICI 118551, respectively) revealed two beta adrenoceptor subtypes in adult kidneys but only the beta-2 subtype in fetal kidneys. Preincubation of renal cortical membranes with either the beta-1 or the beta-2 adrenergic antagonist prior to competition studies in adult kidneys decreased specific binding and resulted in the detection of only one beta adrenoceptor subtype. Preincubation of fetal kidneys with the beta-1 adrenergic antagonist did not affect binding characteristics; preincubation of fetal kidneys with the beta-2 adrenergic antagonist markedly decreased specific binding from 64 +/- 2% (n = 4) to 29 +/- 2% (n = 3) (P less than 0.05). Analysis of Rosenthal plots revealed similar beta adrenoceptor densities and affinities between fetal and adult kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗

PubMed1990

Neural control of renal hemodynamics and function during development.

This review summarizes our current understanding of the role of the renal sympathetic nervous system during development. Recent evidence suggests that renal innervation appears early during fetal life and may play an important role in promoting cellular development. It has also been observed that renal nerve stimulation decreases renal blood flow and increases renal vascular resistance in fetal sheep, but to a lesser extent than in newborn and adult sheep. Moreover, it has been shown that, contrary to previous findings in adult animals, renal nerve stimulation during alpha-adrenoceptor blockade induces renal vasodilation in fetal and newborn sheep, but not in adult sheep. Recent studies have also demonstrated that renal nerves modulate the natriuretic response to a saline load in newborn lambs and influence sodium reabsorption in near-term fetal sheep. The role of renal nerves and neuronally released norepinephrine on renin secretion in the developing kidney is discussed. Finally, it is suggested that efferent renal sympathetic nerve activity might influence fetal renal hemodynamics during stressful conditions.

Humans↗

PubMed1990

Effect of intrauterine growth retardation on renal function on day one of life.

We measured inulin clearance per kilogram, fractional sodium excretion per kilogram, osmolality, and urinary prostaglandin concentration in seven growth-retarded neonates and six appropriately grown neonates matched for gestational age during the first 24 hours of life to determine the effect of fetal growth retardation on renal function. There was a nonsignificant reduction in inulin clearance per kilogram in the growth-retarded neonates (p = 0.11). Inulin clearance correlated with gestational age in both groups. It was significantly correlated with birthweight in the growth-retarded group (p less than 0.05) but did not reach significance in the control group (p less than 0.06). Fractional sodium excretion was significantly higher in the growth-retarded fetuses (p less than 0.05). This increase was not explainable by differences in mean blood pressure and intravenous fluid intake, although differences in urinary prostaglandin concentrations during the study interval may be involved. In conclusion, we have demonstrated that growth retardation is associated with impaired renal maturation, which during the first 24 hours of life is manifest as decreased glomerular filtration rate and increased sodium excretion.

Fetal Growth Retardation↗

PubMed1990

Role of renal sympathetic nerves in response of the ovine fetus to volume expansion.

To investigate the role of renal sympathetic nerves in the fetal response to hypervolemia, studies were carried out in conscious, chronically instrumented fetal sheep aged 137-142 days of gestation. Bilateral renal denervation (n = 9) or sham surgery (n = 8) was carried out under halothane anesthesia 3-6 days before experiments. Bilateral renal denervation did not alter basal fetal renal hemodynamics, glomerular filtration rate (GFR), or Na+ excretion. Volume expansion with 6% Dextran 70 (18 ml/kg) was associated with a fall in fetal hematocrit, a sustained increase in mean arterial blood pressure, and a sustained diuresis and natriuresis. There was no significant change in GFR during fetal hypervolemia from control levels of 4.51 +/- 0.74 ml/min (intact) and 4.43 +/- 0.43 ml/min (denervated). Atrial natriuretic factor increased from 144 +/- 34 to 464 +/- 134 pg/ml, and plasma renin activity decreased from 5.15 +/- 1.7 to 3.04 +/- 1.0 ng.ml-1.h-1 in intact animals, within 30 min of completion of the dextran infusion. Similar changes occurred in denervated fetuses. Plasma aldosterone levels remained constant in intact and denervated fetuses during hypervolemia at control levels of 40.8 +/- 5.4 and 59.3 +/- 8.4 pg/ml, respectively. These findings suggest that renal sympathetic nerves do not influence basal renal hemodynamics or function and do not appear to play an important role in the natriuretic response to volume expansion during fetal life. This can be explained by a low tonic renal nerve activity before birth.

Animals↗

PubMed1990

Novel recordings of renal sympathetic nerve activity in conscious fetal sheep and newborn lambs.

This study describes a technique for measuring efferent renal sympathetic nerve activity (RSNA) during the perinatal period. Experiments were carried out in four chronically instrumented fetal sheep (gestational age, 134-140 days) and 6 newborn lambs (postnatal age, 3-7 days). Surgery, performed under halothane anesthesia, consisted of routine catheter insertions and placement of a Doppler flow probe around the left renal artery. In addition, bipolar platinum electrodes were placed on a branch of the left renal postganglionic nerve. At least 24 h after surgery RSNA was measured in conscious fetal and newborn animals. RSNA was pulse synchronous, reduced with pressor agents, and completely inhibited during ganglionic blockade. Using this method, we have provided direct evidence of efferent renal sympathetic nerve traffic in utero and in the immediate postnatal period. This technique opens new avenues into the investigation of the role of the sympathetic nervous system during the perinatal period.

Animals↗