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Biomedical subjects

J E Robillard

Publications and source records attributed to J E Robillard.

At least 73 records · Page 4Linked to original sources
PubMed1990

Developmental changes in sodium nitroprusside and atrial natriuretic factor mediated relaxation in the guinea pig aorta.

Sodium nitroprusside (SNP), a nonreceptor mediated stimulant of soluble guanylate cyclase, and atrial natriuretic factor, a receptor-dependent stimulator of particulate guanylate cyclase, mediate relaxation responses by increasing intracellular cGMP. This in vitro study was designed to compare the ontogeny of relaxation responses to SNP and atrial natriuretic factor in the guinea pig thoracic aorta. Aortic rings from fetuses at 55-60 d gestation (term = 68 d), 1- to 3-d-old newborn, and 12-wk-old adult Hartley guinea pigs were mounted in an organ bath, bathed in Kreb's solution, and connected to a force-displacement transducer to measure isometric tension. Relaxation responses to SNP and atriopeptin III were studied with the vessels at optimal resting tension and after preconstriction with an EC85 concentration of norepinephrine. SNP-mediated relaxation showed a significant increase in sensitivity with development among the three age groups (p less than 0.05). Methylene blue, an inhibitor of soluble guanylate cyclase, produced no inhibition of relaxation to SNP in fetal aortae, significantly decreased responses along the straight portion of the concentration-response curve in newborn aortae (p less than 0.05), and significantly shifted the concentration-response curve to the right (p less than 0.05) in adult aortae; but did not prevent vessels from relaxing almost 100% in any age group. However, atriopeptin III-mediated responses were similar in the three age groups and were unaffected by methylene blue. These results suggest that 1) sensitivity to SNP increases with age from fetal through adult life; 2) relaxation mediated by atriopeptin III is similar during development; 3) methylene blue does not affect SNP mediated relaxation in fetuses but progressively decreases sensitivity to SNP in newborns and adults; and 4) methylene blue does not affect atriopeptin III-mediated relaxation in any age group.

Aging↗
PubMed1990

Developmental regulation of angiotensinogen gene expression in sheep.

It has been suggested that the liver is not the main source of angiotensinogen during fetal life in rats, but that the kidney is an important site of fetal angiotensinogen synthesis. In an effort to determine if this phenomenon is specific to the rat or applicable to other species, we compared the ontogenic changes in hepatic and renal angiotensinogen mRNA expression in fetal (60, 90, 118, and 138 d of gestation, term being 145 d), newborn (7 d postnatal), and adult sheep. Total RNA was extracted, subjected to Northern blotting and hybridized using a full-length rat radiolabeled antisense RNA. Angiotensinogen mRNA sequences were detected in all fetal liver samples and appeared to increase 3-fold from 60 to 138 d gestation and then to decrease after birth. In contrast, angiotensinogen mRNA could not be detected in renal cortical tissue of 118 or 138 d fetuses, or newborn or adult sheep. We conclude that, unlike in the rat, liver angiotensinogen gene expression is detectable during the 2nd trimester of gestation in sheep and is developmentally regulated. Furthermore, in contrast to the fetal rat, angiotensinogen mRNA sequences were undetectable in fetal sheep kidney.

Angiotensinogen↗
PubMed1989

Effect of acute intravascular volume expansion on human fetal prostaglandin concentrations.

Direct fetal intravascular transfusion is well tolerated by the human fetus. However, the rapid transfusion of high-hematocrit blood should increase vessel distention and the flow shear force. Each is known to stimulate the release of prostacyclin. We measured prostaglandins E2 and F2 alpha and the stable metabolite of prostacyclin, 6-keto-prostaglandin F1 alpha, by radioimmunoassay before, at the estimated midway point of, and at the completion of 40 umbilical venous transfusions performed because of immune hemolytic anemia. Umbilical venous pressures corrected for amniotic fluid pressure were measured at similar intervals during nine of the procedures. The mean (+/- SEM) length of gestation at transfusion was 29 +/- 1 week, opening hematocrit 23% +/- 1%, and total volume of 70% hematocrit red blood cells transfused 83 +/- 5 ml. 6-Keto-prostaglandin F1 alpha was the principal circulating fetal prostanoid and its concentration was unrelated to gestational age. Intravenous transfusion was associated with an 84% increase in 6-keto-prostaglandin F1 alpha (p = 0.03) and a 68% increase in prostaglandin E2 (p less than 0.05). The rise for each strongly correlated with the rise in the fetal umbilical venous pressure (6-keto-prostaglandin F1 alpha, r = 0.94, p = 0.0005; prostaglandin E2, r = 0.81, p less than 0.03). We conclude that 6-keto-prostaglandin F1 alpha is the principal circulating prostaglandin in the human fetus and that the release of venodilator prostaglandins may be one reason the human fetus can tolerate a large increase in intravascular volume without obvious sequelae.

Blood Transfusion, Intrauterine↗
PubMed1989

Does furosemide alter the hemodynamic response to rapid intravascular transfusion of the anemic fetal lamb?

The purpose of this study was to define the hemodynamic response to rapid intravascular transfusion of the anemic fetal lamb and to determine whether furosemide alters that response. Sixteen experiments were performed in nine chronically instrumented gravid ewes between 0.8 and 0.9 of timed gestation. On day 1 of each experiment, each fetus was subjected to hemorrhage (40 ml/kg of estimated fetal weight) over 1 hour. On day 2, plasma was withdrawn from the stored fetal blood until the hematocrit was approximately 70%, and the packed red blood cells were returned to the fetus intravenously over 10 minutes. Each fetus received either furosemide (2 mg/kg) or control saline solution intravenously at time zero and again at 5 minutes. The order of experiments was randomly determined for each animal. Hemorrhage resulted in a similar decrease in fetal hematocrit in the two groups. The mean +/- SEM fetal hematocrit before hemorrhage was 38 +/- 3% in the furosemide group (n = 8) and 36 +/- 2% in the control group (n = 8). On day 2, the mean +/- SEM fetal hematocrit before transfusion was 28 +/- 2% in the furosemide group and 25 +/- 1% in the control group. There was no significant difference between groups in the fetal hemodynamic response to transfusion. At the end of the transfusion, the fetal central venous pressure had increased from 4.9 +/- 0.5 to 6.2 +/- 0.5 mm Hg in the furosemide group (p = 0.01) and from 3.9 +/- 0.2 to 5.8 +/- 0.3 mm Hg in the control group (p = 0.0001). Fetal mean arterial pressure increased from 42 +/- 1 to 50 +/- 1 mm Hg in the furosemide group (p = 0.0001) and from 40 +/- 1 to 46 +/- 1 mm Hg in the control group (p = 0.0007). Fetal heart rate decreased from 187 +/- 2 to 169 +/- 5 beats/min in the furosemide group (p = 0.004) and from 188 +/- 4 to 170 +/- 5 beats/min in the control group (p = 0.0008). Transfusion did not significantly change fetal pH in either group. At 120 minutes, the fetal PO2 had increased from 17 +/- 1 to 19 +/- 1 mm Hg in the furosemide group (p = 0.03) and from 19 +/- 1 to 21 +/- 2 mm Hg in the control group (p = 0.05). We conclude that rapid transfusion of the anemic fetal lamb resulted in modest increases in fetal central venous pressure and mean arterial pressure.(ABSTRACT TRUNCATED AT 400 WORDS)

Anemia, Hemolytic↗
PubMed1989

Endocrine control of electrolyte balance during development.

The endocrine control of electrolyte balance during development is reviewed. It is suggested that the high urinary sodium excretion observed in premature infants may be secondary to the immaturity of the adrenal gland to adequately increase the secretion of aldosterone (Sulyok et al, 1979b), and to the inability of the distal tubule to respond appropriately to a rise in circulating aldosterone levels (Sulyok et al, 1979a). On the other hand, the elevated plasma aldosterone levels observed in term newborn infants may play an important role in the blunted response of the newborn kidney to saline loading (Sulyok et al, 1979a; Spitzer, 1982). The ability of ANP to induce a natriuresis and to contribute to fluid and electrolyte homeostasis during development has been investigated. It has been found that the immature kidney is less responsive to ANP than later in life (Chevalier et al, 1988; Robillard et al, 1988). On the other hand, it has been suggested that a rise in plasma ANP during the first five days of life may contribute to the physiological weight loss associated with the extracellular volume contraction occurring shortly after birth (Tulassay et al, 1987). The role of glucocorticoids, prostaglandins and the kallikrein-kinin system in regulating electrolyte balance during development is also reviewed.

Endocrine Glands↗
PubMed1989

Ontogeny of isoproterenol-stimulated renin secretion from sheep renal cortical slices.

The ontogeny of renin secretion from renal cortical slices was studied in two groups of fetal (107-109 days of gestation and 131-136 days of gestation; term is 145 days), newborn (3-9 days old), and adult nonpregnant sheep. Isoproterenol (ISO; 10(-8)-10(-5) M) significantly increased active renin secretion in all age groups (P less than 0.05), with newborns having the highest values at all concentrations. However, the percent changes in active renin secretion were similar among all ages. Inactive renin secretion also increased with ISO stimulation, with newborns having the highest rate of inactive renin secretion. The percent of total renin in the active form differed among ages, ranging at base line from 60 +/- 10% in fetuses at greater than 130 days of gestation to 88 +/- 6% in fetuses at less than 110 days of gestation (P less than 0.05). Propranolol (1 microM) inhibited ISO (10(-6) M)-stimulated active renin secretion at all ages. On the other hand, the prostaglandin (PG) synthase inhibitor aspirin (1.6 x 10(-5) M) did not inhibit ISO (10(-6) M)-mediated increases in active renin secretion in fetal (greater than 130 days of gestation) kidney slices and produced values intermediate between base line and ISO alone in newborns and adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1989

Ontogeny of neuronally released norepinephrine on renin secretion in sheep.

The role of renal nerves and norepinephrine release on renin secretion during fetal and postnatal maturation has not been studied. Experiments were performed to determine the effect of veratridine, a substance known to promote norepinephrine release from nerve terminals, on active and inactive renin secretion from renal cortical slices of fetal (134-138 days gestation; term is 145 days), newborn (4-9 days of age), and adult nonpregnant sheep. Veratridine (10-300 microM) significantly increased active renin secretion and produced a small but nonsignificant rise in inactive renin secretion in all three groups of animals (P less than 0.05). The percent rise in active renin secretion during veratridine stimulation was similar among all groups. Veratridine-stimulated (300 microM) active renin secretion was antagonized by tetrodotoxin (0.5 and 5.0 microM) and DL-propranolol (1 microM) in fetal renal cortical slices. However, neither tetrodotoxin nor propranolol completely inhibited the stimulatory effect of veratridine on active renin secretion. These results suggest that 1) norepinephrine released from nerve terminals may regulate active renin secretion early during development; 2) the effect of veratridine on active renin secretion was similar in fetal, newborn, and adult sheep; 3) veratridine had no significant effect on inactive renin secretion; and 4) active renin secretion due to depolarization of nerve terminals in fetal sheep is dependent on activation of beta-adrenoceptors as it is in adults.

Aging↗
PubMed1989

Role of renal nerves in response to volume expansion in conscious newborn lambs.

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.

Aldosterone↗
PubMed1989

Arginine vasopressin and acute, intravascular volume expansion in the human fetus.

There is presently no information concerning the ontogeny and control of arginine vasopressin (AVP) in the human fetus. AVP was measured in 22 nonanemic control fetuses and 7 fetuses with hemolytic anemia undergoing 13 intravascular transfusions. Each transfused fetus received pancuronium (0.3 mg/kg) and furosemide (2 mg/kg). Compared to the control group of nonanemic fetuses with hemolytic disease, AVP was significantly lower in the anemic fetus prior to transfusion (2.6 +/- 0.4 microU/ml versus 10.4 +/- 4.1 microU/ml, p less than 0.05). This suggests that hemolytic anemia is associated with a relative increase in fetal intravascular volume. Intravascular transfusion was associated with a significant increase in AVP (p less than 0.05). These findings could not be explained by changes in either blood pressure, plasma osmolality, or fetal oxygenation.

Anemia, Hemolytic↗
PubMed1989

Renal hemodynamic response to atrial natriuretic factor in fetal and newborn sheep.

We have previously demonstrated that systemic atrial natriuretic factor (ANF) infusion induced a renal vasoconstrictor response in fetal and newborn sheep. The present study was designed to test the hypothesis that the fetal and neonatal renal vasculatures do, in fact, vasodilate in response to ANF but that this effect is negated by vasoconstrictor compensatory mechanisms when ANF is infused systemically. To test this hypothesis, the renal hemodynamic response to intrarenal infusion of ANF was studied in chronically instrumented fetal (125-135 d of gestation; term 145 d) and newborn (8-15 d) sheep. Intrarenal infusion of ANF (0.125 to 4.0 micrograms/kg of body wt in fetuses and 0.25 to 8.0 micrograms/kg in newborns) had no significant effect on mean arterial blood pressure and heart rate. However, ANF produced a concentration-dependent increase in renal blood flow velocity (F = 40.9, p less than 0.001) and a decrease in renal vascular resistance (F = 38.3, p less than 0.001) in both groups. The magnitude of changes in renal blood flow velocity and renal vascular resistance expressed as percentage of changes (% delta) from control values, were similar (p greater than 0.05) in both fetal and newborn sheep during intrarenal infusion of ANF. These results demonstrate that ANF exerts direct vasodilator action on the fetal and neonatal renal vasculature and that the renal vasoconstriction previously observed during systemic infusion of ANF was probably secondary to activation of compensatory mechanisms.

Animals↗
PubMed1989

Regional variation of postjunctional alpha-adrenoceptor responses in the developing renal vascular bed of sheep.

Postjunctional alpha 1- and alpha 2-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 at their optimal resting tension and responses to phenylephrine (alpha 1-adrenoceptor agonist) and guanabenz and UK14304 (both alpha 2-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 alpha 1-adrenoceptor stimulation than to alpha 2-adrenoceptor stimulation, whereas venous segments develop similar isometric tension to alpha 1- and alpha 2-adrenoceptor stimulation. The segmental renal artery develops more isometric tension to alpha 2-adrenoceptor stimulation than the main renal artery. No large developmental differences exist among vessels in the sensitivity (concentration required for half maximal response, ED50) to alpha-adrenoceptor stimulation except for the renal vein with alpha 2-adrenoceptor stimulation. Maximum isometric tension corrected for vessel cross-sectional area decreases with age for all vessels with both alpha 1- and alpha 2-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 alpha 1- and alpha 2-adrenoceptors mediate vasoconstriction in the renal circulation, they may do so at different sites.

Age Factors↗
PubMed1989

Atrial natriuretic factor during fetal and postnatal life: a review.

This review summarizes current understanding of the role of atrial natriuretic factor (ANF) during fetal and postnatal life. The cardiac localization of ANF synthesis changes during development from ventricular to predominantly atrial cardiocytes. ANF is present as a circulating hormone during fetal life and fetal plasma ANF clearance rates and production rates are higher than in adults. ANF is a natriuretic hormone in fetal and newborn animals. However, unlike the adult, this natriuresis does not appear to be related to suppression of the renin-angiotensin system. During fetal life, ANF levels can be increased through both atrial distension and humoral influences. Hence, mechanisms of ANF release during development appear to be similar to those present at maturity.

Aldosterone↗
PubMed1988

Dopamine receptors in the developing sheep kidney.

These studies were designed to characterize dopamine receptor density and affinity in kidneys removed from sheep of varying ages (fetal, newborn, and adult) using radioligand binding methods. Three different radioligands were used: the specific dopamine-1 antagonist 3H-SCH 23390, the dopamine-1/dopamine-2 antagonist 3H-haloperidol, and the dopamine-2 antagonist 3H-spiroperidol. The specific binding of 3H-haloperidol and 3H-spiroperidol was saturable with time and ligand concentration, being indicative of dopamine receptors. The specific binding of the dopamine-1 selective radioligand 3H-SCH 23390 was also saturable with time but displayed several points of saturation with increasing ligand concentration. The specific binding of 3H-haloperidol, which had a low affinity and is indicative of dopamine-1 receptors, showed no age-related changes in maximum receptor density or affinity. On the other hand, the maximum receptor density of dopamine-2 receptors measured by 3H-spiroperidol decreased with age. The observations that renal dopamine-1 receptor density or affinity do not change with maturation are in agreement with our previous studies that showed no age-related changes in dopamine-receptor-mediated renal vasodilatation in sheep. The significance of the decrease in renal dopamine-2 receptor density with age remains to be determined.

Animals↗
PubMed1988

Atrial natriuretic factor, digoxin-like immunoreactive substance, norepinephrine, epinephrine, and plasma renin activity in human fetuses and their alteration by fetal disease.

We measured five hormones presumably involved in fetal homeostasis in specimens obtained by cordocentesis for clinical indications from 106 fetuses. Norms for atrial natriuretic factor, digoxin-like immunoreactive substance, plasma renin activity, norepinephrine, and epinephrine were derived from fetuses ultimately shown to be free of detectable abnormality. Atrial natriuretic factor, digoxin-like immunoreactive substance, and plasma renin activity were unrelated to umbilical vessel source or gestational age. Digoxin-like immunoreactive substance was directly related to PCO2 (r = 0.63, p = 0.02). Digoxin-like immunoreactive substance level was elevated in all fetal disease states studied except isoimmunization. The level of atrial natriuretic factor was elevated in fetuses with immune hydrops (NS). Norepinephrine and epinephrine levels were higher in the umbilical artery than in the vein (p = 0.05 and 0.006, respectively). There was a significant correlation between norepinephrine and gestational age in normal fetuses (r = 0.7637, p less than 0.025) and between both catecholamines and many of the respiratory blood gas measurements, with pH and PCO2 being the major determinants. Most disease states were associated with an elevated norepinephrine concentration. There was a negative correlation between plasma renin activity and base deficit (p less than 0.0001). Plasma renin activity was elevated in fetuses with idiopathic growth retardation and nonimmune hydrops (p less than 0.05 for each). In summary, fetal homeostasis as reflected by these five hormones was altered by a variety of disorders. With these baseline values the effects of direct or indirect fetal therapy can begin to be studied.

Atrial Natriuretic Factor↗
PubMed1988

Transplacental passage and hemodynamic effects of esmolol in the gravid ewe.

Using a chronic maternal-fetal sheep preparation, the authors determined the transplacental passage and the hemodynamic changes consequent to maternal administration of esmolol. Fifteen experiments were performed in six chronically instrumented pregnant ewes near term. Each animal received esmolol iv, 500 micrograms.kg-1.min-1, for 4 min and then 300 micrograms.kg-1.min-1 for 6 min. Maternal and fetal blood esmolol concentrations (mean +/- SEM) were 1.2 +/- 0.28 and 0.1 +/- 0.03 micrograms/ml, respectively, at the completion of the infusion, and 0.03 +/- 0.01 microgram/ml in the mother and not detectable in the fetus 10 min after stopping the infusion. Despite the relatively low blood esmolol concentration in the fetus compared to the mother, the hemodynamic effects in the fetus were similar to those in the mother. The maximal decrease of maternal mean arterial pressure (MAP) and heart rate (HR) were 7 +/- 2 and 14 +/- 3% (mean +/- SEM), respectively (P less than .05). The maximal decrease of fetal MAP and HR were 7 +/- 2 and 12 +/- 3%, respectively (P less than .05). No changes were seen in maternal or fetal acid-base variables, and intra-amniotic pressure was not affected. The authors conclude that esmolol has a rapid but relatively small transplacental passage, and it is eliminated rapidly from both maternal and fetal plasma.

Adrenergic beta-Antagonists↗