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Biomedical subjects

M D Bailie

Publications and source records attributed to M D Bailie.

At least 37 records · Page 2Linked to original sources
PubMed1980

Postnatal development of the renin-angiotensin system in rats.

The purpose of this investigation was to correlate the development of the various enzyme activities associated with the renin-angiotensin system with age-related differences in the steady-state concentrations of angiotensin I (AI) and II (AII). Angiotensin was quantified by radioimmunoassay. Plasma renin activity and concentration increased between birth and 3 wk of age, and declined thereafter to adult values. Renal renin content, on the other hand, increased throughout the first 6 wk of postnatal life. The concentration of AII in plasma also increased following birth; however, maximum concentrations were not attained until 5 wk of age. In contrast, plasma AI did not increase between 3 and 6 wk of age. These data suggest that the steady-state concentration of AII in neonatal rat plasma may be partially limited by the low plasma renin substrate concentration. The increase in AII between 3 and 6 wk of age may reflect the increasing converting enzyme activity.

Aging↗
PubMed1980

Effect of saralasin and indomethacin on renal function in developing piglets.

To investigate the influence of angiotensin II (AII) and renal prostaglandins on neonatal renal hemodynamics and sodium excretion, unanesthetized piglets 1-5, 18-20, and 45-50 days of age were treated with saralasin and indomethacin prior to volume expansion (VE) with isotonic saline. Saralasin did not affect basal renal blood flow (RBF) or the intrarenal distribution of blood flow as calculated as the ratio of outer-to-inner slice counts (O/I) in piglets 1-50 days of age. VE increased fractional sodium excretion equally in all animals. In 1- to 5-day-old piglets, saralasin blunted this natriuresis without affecting renal hemodynamics. Therefore, low neonatal RBF and O/I do not appear to be due to AII. In addition, indomethacin did not change renal hemodynamics in newborn piglets and did not affect the natriuresis after VE in any age group. Indomethacin decreased RBF and increased O/I of conscious 45- to 50-day-old animals. Renal prostaglandins do not appear to be a factor in control of renal hemodynamic in newborn pigs and do not influence the natriuresis in neonates following saline loading.

Aging↗
PubMed1980

Disposition of 5-hydroxytryptamine in lungs of developing rats.

The pulmonary vasculature has been implicated in the clearance of several vasoactive peptides, prostaglandins, and biogenic amines from the circulation. In view of the age-related differences in the metabolism of angiotensin by intact lungs, it was of interest to examine the maturation of 5-hydroxytryptamine (5-HT) disposition by isolated perfused lungs. Lungs from newborn and adult rats were perfused with Krebs bicarbonate buffer containing 0.1 microM 5-[14C]HT and samples of the effluent medium collected and analyzed for 5-HT and metabolite. Adult lungs removed and a greater fraction of perfused 5-HT than did lungs from 7-day-old rats. No age-related difference in monoamine oxidase (MAO) activity was observed; however, lung slices from adult rats incubated with 5-[14C]HT accumulated radiolabel at a greater rate than did slices from lungs of 7-day-old rats. The age-related difference in 5-HT clearance by intact lungs may be attributable to a relative deficiency in the facilitated transport process for 5-HT in newborns and may reflect a general functional maturation of processes associated with pulmonary endothelial cell membranes.

Aging↗
PubMed1980

Release of active and inactive renin by the pig kidney during development.

The release of both active and acid-activatable (inactive), renin was determined in piglets ranging in age from 3 to 53 days. The concentration of active renin in arterial plasma during control periods decreased from 4.4 +/- 1.1 ng/ml in 3--5-day-old animals to 0.7 +/- 0.1 ng/ml in 42-53-day-old animals, while the rate of release of active renin was unchanged (11.8 +/- 5.1 ng/min and 7.5 +/- 3.4 ng/min, respectively). Both isoproterenol and furosemide stimulated release of renin in all age animals while propranolol supressed renin release. The data indicate that the qualitative control of renin release is similar in animals of various ages and stages of development. However, the differences in the concentration of renin in plasma of newborn and more mature animals may depend on factors other than release of renin by the kidney. Newborn animals release both active and inactive renin from the kidney.

Age Factors↗
PubMed1980

Regulation of plasma renin in developing piglets.

Plasma renin activity (PRA) was determined in conscious piglets between 1 and 50 days of age before and after treatment with saralasin and indomethacin. Following drug treatment, animals were volume expanded with isotonic saline. Saralasin increased PRA in piglets 1-5 and 18-22 days of age but not 45-50 days. Neither indomethacin nor VE changed PRA at any age. Volume expansion of saralasin- and indomethacin-treated pigs decreased PRA. Neonatal hyperreninemia does not appear to result from renin release stimulated by prostaglandins or by the absence of angiotensin II negative feedback. In addition, the plasma half-life of renin was not different between young and more mature animals suggesting that immature hapatic metabolism of renin cannot be entirely responsible for the high PRA in newborns.

Age Factors↗
PubMed1980

Effect of furosemide on renal function of the newborn piglet.

The effects of development of renal function on the response of newborns to furosemide was evaluated in an animal model, the newborn piglet. Three ages of piglets were used: 5-day-old, 20-day-old, and 50-day-old. Intravenous administration of furosemide (2 mg/kg) produced a prompt natriuresis in all animals. The natriuresis after furosemide was greatest in the older piglets (110 microEq/min for 50-day-old piglets were 210 microEq/min for 5-day-old piglets). However, the fractional sodium excretion at the peak of the response was near 20% in animals in each age group. Neither the time of peak response nor duration of natriuresis was affected by age. Potassium excretion increased after furosemide and remained elevated after both urine flow and sodium excretion had returned to control. The pattern of potassium excretion was identical for each of the three age groups. Thus, while renal maturation does not markedly affect the response to furosemide, both newborns and older piglets continue to excrete relatively large amounts of potassium after sodium excretion returns to control.

Aging↗
PubMed1979

Development of angiotensin-converting enzyme in fetal rat lungs.

Angiotensin-converting enzyme (ACE) catalyzes rapid hydrolytic cleavage of angiotensin I to form angiotensin II (AII). Inasmuch as converting enzyme activity is present at birth and increases postnatally to adult values it was of interest to determine the prenatal development of ACE. Converting enzyme activity was determined in the 20,000 x g supernatant fraction of lung homogenates using hippuryl-L-histidyl-L-leucine (HHL) as substrate. Hippuric acid liberated by the hydrolysis of HHL was quantified spectrophotometrically. ACE activity was first detectable at 18 days of gestation and increased fourfold prior to birth (21 days gestation). Pulmonary ACE activity of 1-day-old animals was twice that of fetuses at day 20 of gestation; however, this increase did not appear to result from ventilation alone. The Michaelis-Menten constant for fetal ACE (2.0 mM HHL) was not different from that calculated for ACE of adult rat lungs (2.6 mM). These data were interpreted to indicate that the age-related increase in ACE activity was due to greater ACE content as opposed to further activation of preexisting enzyme. This increase in fetal ACE activity may play an important role in preparing the renin-angiotensin system for postnatal function.

Animals↗
PubMed1979

Release of active and inactive renin by the porcine kidney.

We studied the relative rates of release of active and inactive renin by the kidney in anesthetized pigs. Renin concentration was determined in arterial and renal venous plasma as follows: (1) before and after stimulation of renin release with isoproterenol or furosemide, (2) after suppression of renin release by extracellular fluid volume expansion, and (3) after administration of propranolol or indomethacin. Inactive renin was activated by dialysis of plasma at pH 3.3 for 24 hours. Renin concentration was estimated by radioimmunoassay determination of angiotensin I after a 3-hour incubation with excess homologous renin substrate. Following isoproterenol, the release of active renin increased from 8 +/- 4 (SEM) to 58 +/- 34 ng/min, and inactive renin increased from 53 +/- 33 to 321 +/- 136 ng/min. Similarly, furosemide stimulated the release of both active and inactive renin. Both forms of renin were suppressed by propranolol or indomethacin. Although changes in renin release following volume expansion were not statistically significant, the direction of change for both forms of renin was similar. Following logarithmic conversion of the rate of release, the plot of active vs. inactive renin formed a straight line. Values for active renin as a percentage of the total renin in simultaneously drawn arterial and renal venous plasma samples were not different. Thus, under the conditions of these experiments, release of active and inactive renin appears to be controlled by similar mechanisms. Both stimulation and suppression of renin release result in parallel changes in release of the two forms. Data on relative amounts of active renin in arterial and renal venous plasma suggest that there is no systemic conversion of the two forms.

Animals↗
PubMed1979

Effect of anesthesia on cardiovascular and renal function in the newborn piglet.

The effects of anesthetic agents, nitrous oxide-oxygen, nitrous oxide-oxygen plus ketamine, pentobarbital sodium and halothane, were determined in piglets 6 to 76 hr of age. After observations of cardiovascular and renal function in the unanesthetized state, the drugs were administered and observations were repeated in the anesthetized state. All of the anesthetics caused a decrease in cardiac output and an increase in total peripheral resistance in the newborn piglet. Both nitrous oxide-oxygen plus ketamine and halothane produced a decrease in heart rate while pentobarbital caused an increase and halothane a decrease in systemic blood pressure. Changes in renal function were minimal. Changes in renal blood flow were inconsistent and renal vascular resistance was not modified by any of the drugs. There was little evidence of redistribution of intrarenal blood flow and no significant changes in glomerular filtration rate or sodium excretion. Plasma renin concentration increased after halothane. It was concluded that changes in renal and cardiovascular function due to anesthesia in the newborn were small. Differences between newborn and adult animals may be related to several factors including the state of development of the autonomic nervous system and species differences used in different studies.

Anesthetics↗
PubMed1978

Angiotensin-converting enzyme in developing lung and kidney.

Angiontensin-converting enzyme (ACE) catalyzes rapid conversion of angiotensin II (AII). This enzyme has been identified in the vascular endothelium of nearly every tissue. Inasmuch as AII is the biologically active component of the renin-angiotensin system, and since age-related differences exist in the renin-angiotensin system, it was of interest to determine converting enzyme activity during development. ACE activity was quantified by measuring the optical density of hippuric acid liberated from hippuryl-L-histidyl-L-leucine (HHL) following incubation with the 20,000 X g supernatant of tissue homogenates. Pulmonary ACE activity of near-term fetal rats was not different than 1-day-old animals. Therafter, ACE activity increased during the first 6 wk postpartum in a biphasic manner. A similar age-dependent increase in converting enzyme activity was observed in rat kidney, mouse kidney, and mouse lung. Substrate affinity of all enzymes measured was similar, suggesting that the age-related increase in activity was due to increased enzyme content. The low activity of ACE in the newborn might function to limit AII production.

Aging↗
PubMed1978

Effects of asphyxia on renal function in the newborn piglet.

This investigation was undertaken to determine the nature of acute alterations in renal function following the production of hypoxemia, hypercarbia, and acidosis in newborn piglets 6-96 hr of age. After completion of the surgical procedure piglets were allowed to recover from the effects of anesthesia. When respiratory dead space was increased arterial oxygen tension decreased whereas arterial carbon dioxide tension and hydrogen ion concentration increased. There was little change in glomerular filtration rate. Total renal blood flow decreased and renal vascular resistance increased significantly (504 +/- 78 mm Hg/liter/mm/m2 to 1422 +/- 504). There was no change in distribution of intrarenal blood flow. Sodium excretion and urinary flow rate demonstrated significant parallel increases following the increase in dead space. Plasma renin concentration increased from 67 to 110 ng/ml.

Animals↗
PubMed1978

Effects of asphyxia on cardiac output and organ blood flow in the newborn piglet.

Experiments were performed on newborn piglets 6--96 hr of age. When the respiratory dead space was increased arterial pO2 decreased and pCO2 increased. During this time cardiac output was unchanged (Fig. 1), while heart rate, respiratory rate, and blood pressure increased (Figs. 2 and 3). After 90 min of asphyxia blood flow to the stomach and small and large intestines decreased. Changes in blood flow were associated with dilatation of segments of the small and large intestine with scattered areas of hemorrhage. Pathologic examination revealed scattered areas of mucosal necrosis (Fig. 6).

Animals↗
PubMed1978

Pharmacological analysis of the action of diuretics in the newborn pig.

The effects of furosemide, ethacrynic acid, hydrochlorothiazide and amiloride on renal function of newborn piglets, 5 to 10 days old, were evaluated. Furosemide and ethacrynic acid were the most effective diuretics. Furosemide infusion at 0.5 mg/kg/hr inhibited reabsorption of 21% filtered sodium and ethacrynic acid, 1 mg/kg/hr, increased fractional sodium excretion to 29%. Hydrochlorothiazide infusion produced a milder natriuresis than furosemide or ethacrynic acid. Infusion of hydrochlorothiazide at 1.0 mg/kg/hr increased fractional sodium excretion from 0.3% during the control period to 7.2%. Furosemide, ethacrynic acid and hydrochlorothiazide each increased potassium excretion to near 20 microEq/min. amiloride (1.0 mg/kg/hr) increased fractional sodium excretion from 0.2% during control period to 2.8% during drug infusion but did not affect potassium excretion. When infused in combination with furosemide and hydrochlorothiazide, amiloride increased the natriuresis and decreased the kaliuresis of both diuretics. It is concluded that the unanesthetized piglet is a good model for renal function of immature mammals and responds to diuretics in a manner qualitatively similar to adults.

Animals↗