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Biomedical subjects

J E Robillard

Publications and source records attributed to J E Robillard.

At least 109 records · Page 6Linked to original sources
PubMed1985

Renal responses to hypoxemia during renin-angiotensin system inhibition in fetal lambs.

The role of the renin-angiotensin system (RAS) in modulating the renal hemodynamic and functional responses to hypoxemia was studied in chronically catheterized fetal lambs (132-143 days gestation; term 145 days) before and during administration of either captopril or [Sar1-Gly8]ANG II. Base-line mean arterial blood pressure decreased significantly after administration of either captopril or [Sar1-Gly8]ANG II. This decrease was associated with a significant decline in renal vascular resistance (RVR) in captopril-treated fetuses, whereas no changes in RVR were observed in [Sar1-Gly8]ANG II-treated fetuses. However, the decline in renal blood flow (RBF) and the rise in RVR associated with hypoxemia in control fetuses were not attenuated significantly during inhibition of the RAS using either captopril or [Sar1-Gly8]ANG II. Moreover neither captopril nor [Sar1-Gly8]ANG II blunted the hypertensive response associated with fetal hypoxemia. The renal functional response to captopril was different from the response observed during infusion of [Sar1-Gly8]ANG II. Administration of [Sar1-Gly8]ANG II produced significant decreases in urinary flow rate (UFR), glomerular filtration rate (GFR), and urinary electrolyte (Na+, K+, Cl-) excretion rates, whereas no changes were observed during captopril infusion. The effects of hypoxemia on renal function were not modified after captopril. However, [Sar1-Gly8]ANG II tended to increase UFR and GFR, but these changes were pressure-dependent and not directly related to inhibition of the RAS. This study suggests that the RAS is not an important mediator of the fetal renal hemodynamic and functional responses to hypoxemia.

Angiotensin II↗
PubMed1985

Effects of aldosterone on urinary kallikrein and sodium excretion during fetal life.

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 less than 115 days gestation (n = 6) and greater than 125 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 greater than 125 days and in the majority of fetuses less than 115 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.

Aldosterone↗
PubMed1984

Developmental aspects of the renal responses to hemorrhage during converting-enzyme inhibition in fetal lambs.

The role of the renin-angiotensin system in modulating the renal hemodynamic and functional responses to reductions of fetoplacental blood volume (8.8-35.5%) was studied in two groups of fetal lambs (less than 120 days and greater than 130 days gestation; term 145 days) during infusion of either captopril (experimental fetuses) or dextrose 5% in water (control fetuses). At high hemorrhage levels (level III), renal blood flow decreased and renal vascular resistance increased significantly in both groups of fetuses (less than 120 days and greater than 130 days), either treated or not treated with captopril. However, at low hemorrhage levels (levels I and II), and contrary to what was observed in young fetuses (less than 120 days), near-term fetuses (greater than 130 days) receiving captopril showed neither significant decreases in renal blood flow nor increases in renal vascular resistance, whereas untreated fetuses of the same gestational ages demonstrated significant decreases in renal blood flow and increases in renal vascular resistance. It was found in both less than 120 day and greater than 130 day fetuses that hemorrhage is associated with a decrease in urinary flow rate and free water clearance accompanied by an increase in urine osmolality and sodium reabsorption. It was shown that captopril does not modify this response. The present study also demonstrated that the blood pressure response to hemorrhage was characterized by a similar decrease in less than 120 day fetuses, whether treated or untreated with captopril. On the other hand, blood pressure did not change in control fetuses greater than 130 days, but decreased slightly in captopril-treated fetuses during hemorrhage. Taken together, the present results tend to suggest that the renin-angiotensin system may be an important modulator of the renal hemodynamic response to low level hemorrhage as fetuses approach term, and may be more important in controlling blood pressure in near-term than in young fetuses.

Aldosterone↗
PubMed1984

Factors controlling aldosterone secretion during hypoxemia in fetal lambs.

Factors modulating the fetal aldosterone response to hypoxemia were studied in three groups of chronically catheterized fetal lambs between 131 and 143 days of gestation (term, 145 days). One group (control group) received an infusion of 5% dextrose in water; the second group (captopril-treated group) was given captopril, an inhibitor of angiotensin-converting enzyme; the third group (captopril plus dexamethasone-treated group) received dexamethasone in addition to captopril. In all groups of fetuses, hypoxemia was associated with a significant increase in plasma K+ concentration (+0.7 +/- 0.1 meq/liter). In control fetuses, changes in plasma aldosterone concentration during hypoxemia correlated closely with changes in plasma K+ concentration r = 0.79; P less than 0.001) and with changes in plasma angiotensin II concentration (r = 0.77; P less than 0.001). In the captopril-treated fetuses, the rise in plasma aldosterone concentration during hypoxemia correlated closely with plasma K+ (r = 0.79; P less than 0.001) but not with plasma angiotensin II values (r = 0.17). No significant correlation was found between percent changes in maternal aldosterone and percent changes in fetal aldosterone during hypoxemia and following recovery (r = 0.36; P greater than 0.1) in captopril-treated fetuses. Administration of dexamethasone to fetuses receiving captopril completely inhibited the rise in plasma aldosterone associated with hypoxemia. Taken together, the present results suggest that the rise in plasma aldosterone during hypoxemia is not related to the level of activity of the renin-angiotensin system but depends probably on the increased secretion of adrenocorticotrophin by the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1984

Developmental aspects of the renal response to hemorrhage during fetal life.

The renal hemodynamic and functional responses to sequential reductions of fetoplacental blood volume were studied in two groups of chronically catheterized fetal lambs: less than 120 d gestation, n = 9 and greater than 130 d gestation, n = 7. Significant decreases in renal blood flow (RBF) and increases in renal vascular resistance (RVR) not associated with changes in glomerular filtration were observed in both groups of fetuses. At the highest level of hemorrhage (level III), the percentage change (% delta) in RBF and RVR tended to be more important in the older group of fetuses (-52 +/- 8% and +155 +/- 58%) than in young fetuses (-38 +/- 6% and +68 +/- 18%). Multiple regression analysis demonstrated that in fetuses less than 130 d the % delta in RBF and RVR correlated more closely with the % delta in plasma arginine vasopressin (AVP) (the partial correlation coefficients being r = 0.61, P less than 0.05 and r = 0.73, P less than 0.01 respectively) than with angiotensin II, norepinephrine, or epinephrine. In fetuses less than 120 d gestation, the % delta in RBF correlated better with the % delta in plasma epinephrine (the partial correlation coefficient being r = 0.52, P less than 0.025) than with any other vasoactive substances. Significant decreases in urinary flow rate and free water clearance and increase in urine osmolality (Uosm) were found in both groups of fetuses. The increase in Uosm correlated closely with the rise in plasma AVP in both groups of fetuses; moreover, the slope of the regression line between plasma AVP and Uosm was similar in less than 120-d (slope 22.2) and greater than 130-d fetuses (slope 33.3), suggesting that the sensitivity of the fetal kidney to AVP is stable during the last trimester of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1983

Renal and adrenal responses to converting-enzyme inhibition in fetal and newborn life.

The renal and adrenal responses to a continuous infusion of the angiotensin-converting enzyme (ACE) inhibitor captopril were studied in 27 chronically catheterized sheep fetuses (less than 120 days gestation, n = 15, and greater than 130 days gestation, n = 12; term being 145 days) and in 12 newborn lambs between 8 and 21 days of age. Total renal blood flow did not change during ACE inhibition. However, the renal vascular resistance decreased significantly in newborn lambs (-21.8 +/- 5.7%) and in fetuses greater than 130 days (-21.7 +/- 4.7%) but not in fetuses less than 120 days. A significant decrease in filtration fraction (-19.2 +/- 6.5%) was observed in newborn lambs. No changes in urinary kallikrein and prostaglandin excretion rate were observed during ACE inhibition in any group of animals. ACE inhibition produced similar declines in blood pressure in both groups of fetuses (-10.2 +/- 3% in fetuses less than 120 days and -9.5 +/- 4.6% in fetuses greater than 130 days) and in newborn lambs (-13.4 +/- 2.1%). The percent changes in plasma renin activity were similar in all groups of animals. However, a significant decline in plasma aldosterone concentration was observed only in newborn lambs (from 130 +/- 31 to 64 +/- 9 pg/ml). These results suggest that the renin-angiotensin system might have physiological significance during maturation, but that this role seems to be more important in near-term fetuses (greater than 130 days) and postnatally than early in gestation.

Adrenal Glands↗
PubMed1983

Glucocorticoid stimulation of blood coagulation factor activities in the fetal lamb.

Blood coagulation factor activities, including factors II, VII, IX, X, XI, and XII, are lower than normal in full-term infants and more severely depressed in premature infants. Previous studies in our laboratory using a fetal lamb model indicated that most coagulation factor activities increase during the latter part of the third trimester of pregnancy. Since glucocorticoid stimulation of the fetus accelerates fetal lung maturation in experimental models and in offsprings of mothers with impending premature labor, we hypothesized that glucocorticoid stimulation might induce increases in blood coagulation factor activities similar to those found near term. Two sets of experiments were carried out in chronically catheterized fetal lambs early in the third trimester (100 to 120 days gestation). In one set of experiments, one twin from each of 10 twin sets was infused with hydrocortisone (2 mg/hr for 48 hr). The twin sibling served as a control. In the other set of experiments, six pregnant ewes were given 15 mg of beta-methasone intramuscularly every 24 hr for two doses. Five pregnant ewes were injected with saline and used as controls. Fetal blood samples were obtained prior to and 48 hr after the start of the hydrocortisone infusions and prior to and 24 hr after the second dose of beta-methasone given to the pregnant ewes. The results of blood coagulation factor activities comparing glucocorticoid-stimulated fetuses with controls demonstrated significant increases in the activities of blood coagulation factors II, V, VII, IX, and X in the stimulated fetuses. There were no significant changes in the activities of factors VIII, XI, or XII. The results confirmed the hypothesis that glucocorticoid stimulation increases many blood coagulation factor activities in the fetus.

Animals↗
PubMed1982

Developmental aspects of the renal kallikrein-like activity in fetal and newborn lambs.

The ontogeny of the renal kallikrein-like activity and the interrelationships between this enzyme and the renin-angiotensin-aldosterone and prostaglandin systems were studied in 43 chronically catheterized sheep fetuses between 104 and 142 days of gestation (term, 145 days) and in 8 chronically catheterized newborn lambs between 5 and 23 days of age. Urinary kallikrein (UKall) excretion rate expressed in absolute values (mEU/hr) or corrected for kidney weight (mEU X hr-1 X gKW-1) or glomerular filtration (mEU X hr-1 X ml GFR-1) increased significantly during fetal maturation and after birth. The rise in UKall during fetal and newborn life was not dependent on an increase in urinary flow rate (r = 0.06). The increase in fetal UKall (mEU X hr-1 X gKW-1) correlated closely with the rise in plasma aldosterone concentration for values above 35 pg/ml (r = 0.72, P less than 0.001). A significant negative correlation was found between UKall (mEU X hr-1 X gKW-1) and log of individual urinary sodium excretion values (r = -0.78, P less than 0.001). No correlation was found between UKall and urinary prostaglandins (PGE, PGF2 alpha) excretion during fetal and newborn life, but UKall correlated closely with the rise in renal blood flow during maturation (r = 0.87, P less than 0.001). The present data suggest that aldosterone is an important regulator of UKall release early during development. It is also suggested that conceptional age is an important factor which may modulate the renal sensitivity to aldosterone-stimulated UKall excretion.

Aldosterone↗
PubMed1982

Comparison of the adrenal and renal responses to angiotensin II fetal lambs and adult sheep.

The adrenal and renal responses to similar increases in plasma angiotensin II (AII) were studied in chronically catheterized fetal lambs (112-131 days gestation: term 145 days) and adult nonpregnant sheep. The rate of AII infusion was adjusted to compare the effect of similar rises in plasma AII concentration between fetuses and adult ewes. Increases in plasma AII were associated with a decrease in plasma renin activity (PRA) in both fetuses (5.55 +/- 1.53 to 2.11 +/- 0.59 ng/ml per hr, P less than 0.05) and adult ewes (1.28 +/- 0.34 to 0.62 +/- 0.16 ng/ml per hr, P less than 0.05), but the percent changes in PRA for similar increases in plasma AII were not different when fetuses were compared to adult ewes. Contrary to the effect of AII on PRA, the increase in plasma AII did not produce parallel changes in plasma aldosterone concentration when fetuses were compared to adult ewes. The percent changes in plasma aldosterone concentration for similar increases in AII concentration were significantly higher in adult ewes (+165 +/- 37%) than in fetuses (+58 +/- 15%)(P less than 0.01). Finally, there were no significant changes in fetal urinary excretion of PGE and PGF2alpha when a significant rise (P less than 0.05) was observed in adult ewes at the highest level of plasma AII concentration. In summary, the present results tend to suggest that there are differences between fetuses and adult ewes in the response to AII, the response being smaller in fetuses.

Adrenal Glands↗
PubMed1982

Blood coagulation changes after hypoxemia: a fetal lamb model.

The effects of fetal hypoxemia on blood coagulation (platelet count, prothrombin time, partial thromboplastin time, fibrinogen, factors II, V, VI, VIII, IX, X, XI, XII, XIII and von Willebrands activities, fibrin degradation products, and fibrin monomer) were evaluated in nine chronically catheterized fetal lambs early in the third trimester of pregnancy (107-110 days gestation). Seven chronically catheterized fetal lambs of similar gestational ages served as controls. The hypoxemic episode (pO2 14 mm Hg) was maintained for 1 hr in the experimental group during which time there were only minimal changes in PCO2, arterial pressure, heart rate, and pH. Epinephrine and norepinephrine levels increased significantly in stressed animals--22 pg/ml pre- to 1025 pg/ml postepinephrine, and 475 pg/ml pre- to 2292 pg/ml postnorepinephrine. There were no significant changes in blood coagulation factor activities related to the hypoxic stress although, one fetus who experienced acidemia did develop a transient increase in fibrin monomer. Slight through significant increases in VIII coagulant activity activity (4.0%), von Willebrand activity (5.9%), and factor XII activity (4.3%) occurred in both the hypoxemic and control fetal lambs. These changes were associated with minimal increases in the white blood cell count (15%) and slight decreases in the mean arterial pressure (3.9 mm Hg) hemoglobin (1.2 g), and hematocrit (2.9%) and may have been related to the blood loss of 25% that occurred as a result of sampling in both groups. There were no differences between the hypoxic and control animals' levels of coagulation factor activities when measured during an 18-day follow-up period except for a slight increase in factor X activity (10%) in the control animals not apparent in the nine hypoxic animals. Thus an episode of severe fetal hypoxemia in the absence of hypotension, acidosis, and hypercarbia does not lead to acute or chronic alterations in blood coagulation factor activities in the fetal lamb.

Animals↗
PubMed1981

Interaction of minoxidil and captopril in the treatment of refractory hypertension.

A case of severe hypertension resistant to multiple drug therapy was controlled with minoxidil, captopril, and propranolol hydrochloride after treatment with these drugs alone or in other combinations had failed. Hyperreninemic hypoaldosteronism with hyperkalemia and acidosis developed after captopril administration was started.

Acidosis↗
PubMed1981

Effects of inhibition of prostaglandin synthesis on fetal renal function.

The role of renal prostaglandin production on the control of renal blood flow (RBF) and renal function was studied in eight chronically catheterized fetal lambs during the last trimester of gestation by using indomethacin as an inhibitor of prostaglandin synthesis. Following administration of indomethacin, RBF decreased significantly (-7.44 +/- 2.04 ml/min) whereas significant increases in filtration fraction (+3.92 +/- 0.85%) and renal vascular resistance (+ 0.41 +/- 0.13 mm Hg . ml-1 . min-1) were observed. Significant changes in glomerular perfusion rate were observed only in the inner portion of the cortex. No changes in GFR were demonstrated. Following administration of indomethacin, significant increases in fetal urinary sodium (+22.2 +/- 7.03 micro E/min) and chloride excretion (+18.2 +/- 6.26 micro E/min) were found despite a decrease in RBF. No changes in potassium excretion were seen. A significant increase in Uosm (+100 +/- 25.9 mOsm/kg H2O) not associated with significant changes in urinary flow rate was also demonstrated following indomethacin. Finally, fetal administration of indomethacin produced a significant decrease in plasma renin activity (-2.70 +/- 0.65 ng/ml/hr) not associated with changes in plasma aldosterone concentration. The present data are consistent with the idea that prostaglandins are important modulators of RBF and renin secretion during fetal life. The inability of indomethacin to render the urine hypertonic indicates that the inability of the fetal kidney to concentrate is probably not due to endogenous activity of the renal prostaglandin system. The increase in sodium chloride excretion with a concomitant reduction of RBF is a pattern not previously reported following inhibition of prostaglandin production. In addition to their effects on RBF and renin release, renal prostaglandins in the fetal kidney may have tubular effects on sodium and chloride absorption that are opposite to those generally ascribed to adult kidneys.

Animals↗
PubMed1981

Developmental aspects of the renal response to hypoxemia in the lamb fetus.

The effects of fetal hypoxemia on renal hemodynamics and renal function were studied in two groups of chronically catheterized young (< 120 days of gestation) and near-term lamb fetuses (> 130 days). Fetal hypoxemia produced, in both groups, a significantly decrease in renal blood flow (RBF) and a significant increase in the filtration fraction. However, the glomerular filtration rate (GFR) did not change significantly suggesting that the renal vasoconstriction associated with fetal hypoxemia was more important at the efferent than at the afferent arteriolar level. In the group of near-term fetuses, the decrease in RBF correlated closely with changes in plasma renin activity (PRA) (r = 0.77). No changes in PRA were observed during hypoxemia in the group of young fetuses. After hypoxemia, reactive hyperemia associated with a significant increase in urinary prostaglandin excretion (PGE and PGF2 alpha) was observed in near-term fetuses but not in young fetuses. It also was demonstrated that fetal hypoxemia produced a significant increase in fetal plasma concentrations of vasopressin associated with an antidiuresis in all but one near-term fetus and in 50% of the young fetuses, suggesting that the ability of the fetal kidney to reabsorb free water is more developed in near-term fetuses. Finally, fetal hypoxemia had no effect on mean arterial pressure and heart rate in young fetuses; however, in near-term fetuses, a significant increase in blood pressure and a decrease in heart rate were observed. In summary, it appears that the response of the fetal kidney to hypoxemia depends on the degree of fetal maturation.

Animals↗
PubMed1981

Development of blood coagulation--a fetal lamb model.

To study the normal development of blood coagulation factor activities in a growing fetus while avoiding the effects of labor and delivery, a chronic fetal lamb model was developed in which serial blood samples from 10 fetuses were studied during the third trimester of pregnancy and 24 hr after birth. Under operating room conditions with sterile technique, a polyethylene catheter to which heparin had been bound to both internal and external surfaces was inserted into the femoral artery of the fetus. The catheter was brought out through a skin pouch to the side of the ewe and enclosed in a zip lock bag. Blood samples were withdrawn from the catheter three times each week for measurement of coagulation factor activities. Levels of coagulation factor activities at birth in noncatheterized animals were not different from those found in catheterized animals except for factor IX activity which was 12% higher in the catheterized animals (0.02 less than P less than 0.05). The patterns of development for each of the coagulation factors were similar in all 10 animals studied. Fibrinogen, prothrombin, and factor VII show a decrease in activity early in the last trimester of pregnancy. Both factors VIII and IX show a significant increase in activity (23% factor VIII and 12% factor IX) associated with the process of delivery. The levels of coagulation factor activities at birth in the lamb relative to adult sheep normals are similar to those found in humans with the exception of factor XIII. Factor XIII is at normal levels in the newborn lamb and is reported to be at levels approximately 50% of the adult level in human infants.

Animals↗