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Biomedical subjects

J B Hook

Publications and source records attributed to J B Hook.

At least 145 records · Page 8Linked to original sources

The effects of maternal protein deprivation on renal development and function in neonatal rats.

This study was undertaken to investigate the effects of pre- and/or postnatal maternal protein deprivation (PD) on renal functional development in the offspring. Pregnant rats were fed either a control (24% protein) or low (8 or 10%) protein diet during gestation and lactation. Progeny of these dams were cross-fostered at birth, yielding four experimental groups: pups born of control dams and nursed by PD or control dams and pups born of PD dams and nursed by control or PD dams. While the effects of prenatal PD on body and kidney growth were negligible, PD during the nursing period appeared to have a more profound effect on body and kidney weight. Renal transport functions, quantified in vitro, were differentially affected by these dietary manipulations. Renal transport capacity for organic acids and bases was depressed in pups nursed by PD dams. Maturation of the renal organic acid transport system was also delayed in these pups. alpha-Aminoisobutyric acid accumulation by renal cortical slices was enhanced only in 10-day old rats stressed by pre- and postnatal maternal PD. Renal gluconeogenic and ammoniagenic capacity was not impaired by these dietary manipulations. No differences in protein or water content of renal cortical slices were observed.

Aminoisobutyric Acids↗

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↗

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↗

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↗

Prostaglandin-forming cyclooxygenase in renal medulla of spontaneously hypertensive rats during development.

Increased activity of prostaglandin synthetase in spontaneously hypertensive rats (SHR) during development has previously been reported. The investigations reported herein utilized an immunofluorescent technique to qualitatively assess the activity of the first enzyme in the PGE2 biosynthetic pathway, the prostaglandin-forming cyclooxygenase (PG-C), in SHR kidneys during development. PG-C antigenicity increased from 4 to 15 weeks in both SHRs and Wistar Kyoto normotensive rats. However, in agreement with our previous in vitro data no difference in PG-C was observed between strains at any age.

Animals↗

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↗

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↗

Effects of polybrominated biphenyls on kidney function and activity of renal microsomal enzymes.

Polybrominated biphenyls (PBBs) cause hepatic microsomal enzyme stimulation and histopathological alterations in several organs, including kidney. Concern about effects of PBBs on the health of newborns has increased after the discovery of PBBs in milk of nursing mothers. Therefore, it was of interest to investigate the effects of PBBs on kidney function and the activity of renal microsomal enzymes in adult and immature animals. Seven and eleven day old pups were treated with a single IP injection of either peanut oil or 150 mg/kg PBBs (FireMaster BP-6) in peanut oil. Adult virgin rats were fed diet containing 0 or 100 ppm PBBs for 30 or 90 days. Treatment with PBBs only retarded weight gain after 90 days exposure. Kidney-to-body weight ratio was not altered by PBBs. Arylhydrocarbon hydroxylase activity was increased while epoxide hydratase activity was decreased (adults) or not affected (immature rats) in kidney following treatment with PBBs. Administration of PBBs had no effect on blood urea nitrogen, the clearance of inulin, p-aminohippurate (PAH), or fractional sodium excretion. Similarly, the in vitro accumulation of PAH and N-methylnicotinamide (NMN) by thin renal cortical slices and ammoniagenesis and gluconeogenesis in renal cortical slices were not affected by PBBs. In conclusion, treatment with PBBs resulted in modification of the activity of renal microsomal enzyme activities but had no detectable effect on renal function.

Animals↗

Potentiation of hepatic and renal toxicity of various compounds by prior exposure to polybrominated biphenyls.

Mice ingesting a standard rodent diet supplemented with polybrominated biphenyls (PBBs) were more susceptible to chlorinated hydrocarbon solvent-induced renal and hepatic damage, as well as the lethal effects of CHCl3 and CCl4, than were mice consuming control diet. As little as 0.025 ml/kg CHCl3 caused a significant increase in serum glutamic oxaloacetic transaminase (SGOT) and blood urea nitrogen (BUN) and a significant decrease in renal cortical slices accumulation of p-aminohippurate (PAH) in PBB-pretreated but not control mice. SGOT and serum glutamic pyruvate transaminase (SGPT) were greater in PBB-pretreated mice than in control mice after 0.125 and 0.005 ml/kg CCl4, respectively. Renal cortical PAH accumulation was greatly reduced in PBB-pretreated but not control mice aftter 0.125 ml/kg CCl4. The solvent-induced decrease in PAH accumulation was also greater in PBB-pretreated mice than in control mice following administration of 1.0 ml/kg trichloroethylene (TRI) and 0.15 ml/kg 1,1,2-trichloroethane (TCE).

Animal Feed↗

Factors affecting tissue aluminum concentration.

Elevated concentration of aluminum has been reported in serum, whole blood and tissue samples of patients with renal insufficiency. Evidence incriminating aluminum as a neurotoxin among the dialysis population is strong. The source of this aluminum has not been clearly defined, although both gastrointestinal and parenteral routes may be involved. Data from this laboratory suggest that an effect of parathyroid hormone on tissue aluminum burdens may, in part, explain why only certain patients exposed to high dialysate aluminum develop the dialysis encephalopathy syndrome and the occasional occurrence of this syndrome in the absence of dialysis or increased dialysate aluminum.

Administration, Oral↗