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Biomedical subjects

F G Smith

Publications and source records attributed to F G Smith.

At least 55 records · Page 3Linked to original sources
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

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↗
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

Measurement of net sodium intake by the ovine fetus with oesophageal ligation.

1. If the fetal sheep is in sodium balance, then the net intake of sodium is equal to the sum of the losses of sodium in fetal urine and lung liquid plus the rate of deposition of sodium with growth. 2. In seven fetal sheep with oesophageal ligation net sodium intake was 23.1 +/- 2.8 (s.e.m.) mumols/min per kg; 11.8 +/- 1.4 mumols/min per kg was excreted by the lungs and 8.7 +/- 2.3 mumol/min per kg was excreted by the kidneys. The excretion of sodium by the lungs accounted for 52.8 +/- 4.8% of the total amount of sodium; the excretion of sodium by the kidneys accounted for 34.9 +/- 5.4% and the calculated variable, that is, sodium deposited due to growth was 12.3 +/- 1.4%. 3. All but one fetus excreted more sodium from the lungs than from the kidneys. There was no relationship between the clearance of sodium by the lungs and net sodium intake but there was a direct relationship between renal sodium clearance and net sodium intake (r = 0.92, P less than 0.005). This suggests that fetal urinary sodium excretion is dependent upon net sodium intake by the fetus. This animal model shows that normally there must be sodium fluxes from allantoic and/or amniotic cavities to either the fetus or the ewe.

Animals↗
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

Comparison of renal function in term fetal sheep and newborn lambs.

Renal function was measured in fetal sheep, in neonates following delivery by caesarean section, and in lambs in the first week of life. The most marked changes in renal function following delivery were an increase in glomerular filtration rate from 4.59 +/- 0.27 ml/min (n = 13) to 6.94 +/- 1.00 ml/min (n = 12), a decrease in urine flow, sodium and osmolar excretion rates and an increase in urinary osmolality. Fractional sodium reabsorption increased from 95.5 +/- 0.79% (n = 13) in the fetus to 99.4 +/- 0.14% (n = 12, p less than 0.001) in lambs aged 24 h or more; fractional osmolar reabsorption rose from fetal levels of 92.3 +/- 0.84% (n = 13) to 96.5 +/- 0.52% (n = 11; p less than 0.001) in lambs aged 24 h or more. Potassium excretion and fractional potassium reabsorption did not alter after birth. Urinary osmolality increased from 175 +/- 20.4 mosm/kg H2O (n = 14) to 524 +/- 45.6 mosm/kg H2O (n = 16; p less than 0.001) in lambs aged 24 h or more, and free water clearance decreased from 0.308 +/- 0.06 ml/min (n = 13) to -0.067 +/- 0.03 ml/min (n = 15; p less than 0.001). Since the above changes occurred within 24 h of delivery, they represent rapid adjustments by the kidney to lack of a placental supply of fluid and electrolytes.

Animals↗
PubMed1989

Effect of hypoxia and catecholamines on the habituation rates of chronically catheterized ovine fetuses.

Integrated electromyographic, electrocortical (ECoG) and electro-ocular activity were recorded in 13 chronically prepared fetal sheep (130-145 days). Fetal movements and the rate of habituation to repeated suffusions of cold saline against the fetal skin were recorded. Experiments were repeated during an intravenous infusion of noradrenaline to the fetus (0.4 microgram/kg estimated fetal weight/min) and during hypoxia induced by altering the oxygen content of the inspired air to the ewe to 9%. Repeated stimulation with cold saline resulted in an increase in fetal movements (p = 0.009). The number of stimuli for habituation was similar in high-voltage and in low-voltage ECoG activity. The rate of fetal habituation was significantly faster during the infusion of noradrenaline compared with control measurements (p = 0.009). During hypoxia, the number of spontaneous fetal movements prior to stimulation decreased (p = 0.002). Habituation rates were also faster during hypoxemia compared with control measurements (p = 0.003). These findings may help to explain the rapid habituation rates seen in some human fetuses in at 'at risk' pregnancies.

Acoustic Stimulation↗
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

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

Effects of maternal hyperglycemia on fetal renal function in sheep.

The effects of maternal hyperglycemia on fetal renal function were investigated in 10 chronically catheterized fetal sheep after the infusion of 100 g of glucose into the ewe over 30 min. Fetal blood glucose levels rose (P less than 0.001) within 15 min of completing the glucose infusion from 15.75 +/- 2.8 to 195.4 +/- 18 (SE) mg/dl (n = 10). There was a significant increase in fetal glomerular filtration rate (P less than 0.05) from 2.73 +/- 0.41 to 3.65 +/- 0.40 (SE) ml/min (n = 10) within 1.5 h of the infusion of glucose into the ewe. Urine flow rate increased from 0.38 +/- 0.06 to 0.63 +/- 0.12 (SE) ml/min (n = 10, P less than 0.001), and sodium excretion increased from 18.42 +/- 7.21 to 38.4 +/- 13.7 (SE) mumol/min (n = 10, P less than 0.002) within 2.5 h of the infusion of glucose into the ewe. The fraction of the filtered load that was excreted (urine flow rate divided by glomerular filtration rate) also increased (P less than 0.01) as did the fraction of the osmolar load (P less than 0.002). Glycosuria occurred in all fetuses within 30 min of the infusion of glucose into the ewe, and glucose excretion reached 26.16 +/- 12.36 (SE) micrograms/min (n = 8) after 1.5 h. These findings of diuresis, natriuresis, and glycosuria in response to hyperglycemia are evidence that an increased delivery of fluid into the amniotic cavity might occur after a rise in fetal plasma glucose levels.

Animals↗
PubMed1988

Changes in renal function following delivery of the lamb by caesarean section.

Six lambs were delivered by caesarean section at 139 to 145 days of gestation. Birth was associated with a rise in glomerular filtration rate from 4.81 +/- 0.62 to 5.90 +/- 0.74 ml/min and a transient natriuresis secondary to a fall in fractional sodium reabsorption from 93.1 +/- 3.94 to 88.3 +/- 2.29%. This study indicates that in the immediate postnatal period, glomerulotubular balance is disturbed.

Animals↗
PubMed1987

Clenbuterol, a beta agonist, induces growth in innervated and denervated rat soleus muscle via apparently different mechanisms.

Dietary administration of the anabolic agent, clenbuterol, has already been shown to inhibit or reverse denervation-induced atrophy in rat soleus muscles. We now show that the ameliorative effects of clenbuterol in denervated rat muscles are due principally to a large increase in protein synthesis. This results from both an increase in protein synthetic capacity and a normalised translational efficiency. The responses of innervated and denervated muscles are therefore fundamentally different, the changes in denervated muscles being reminiscent of the classical pleiotypic response of cells to growth factors.

Animals↗
PubMed1987

The effect of the anabolic agent, clenbuterol, on overloaded rat skeletal muscle.

The dietary administration of clenbuterol to young male rats has been shown to produce a muscle specific hypertrophic growth response. This paper demonstrates that the combined effect of drug treatment and hypertrophic stimulus induced by tenotomy produced an additive effect on muscle growth. This effect was demonstrated in terms of both muscle composition (protein and RNA) and fibre size.

Animals↗
PubMed1987

Propranolol apparently separates the physical and compositional characteristics of muscle growth induced by clenbuterol.

The effect of propranolol on clenbuterol-induced changes in muscle fibre size and protein content were studied. Propranolol did not inhibit the ability of clenbuterol to stimulate protein accretion but reduced the increase in muscle fibre size. The compositional and physical characteristics of clenbuterol-induced muscle growth thus appeared to be separated by propranolol.

Animals↗
PubMed1987

The effect of maternal hyperglycemia on acid base balance and lung liquid production in the fetal sheep.

In 10 chronically catheterized fetal sheep, the effects of 100 g of glucose infused (intravenous) to the pregnant ewe on lung liquid production and acid-base status were investigated. Maternal and fetal hyperglycemia occurred within 15 min of the infusion of glucose. There was a significant increase in fetal PCO2 from 41.67 +/- 1.00 to 46.89 +/- 1.83 mm Hg and a decrease in fetal arterial pH from 7.42 +/- 0.016 to 7.33 +/- 0.026 (n = 7). This acidosis was probably the result of fetal lactacidemia. There was also a decrease in fetal PO2 (p less than 0.001) following the infusion of glucose to the ewe. This, along with the acidosis, might account for the increased risk of unexplained fetal death in the diabetic pregnancy especially near term. Following the infusion of glucose to the ewe there was an increase in maternal plasma osmolality by 16 +/- 3.35 mosmol/kg (n = 9) and in fetal plasma osmolality by 14 +/- 2.64 mosmol/kg (n = 9; p less than 0.001). Fetal lung liquid production fell from 0.195 +/- 0.04 to 0.093 +/- 0.02 ml/min (n = 6; p less than 0.001). There was no change in the excretion of osmol by the lungs. The decreased lung liquid production was probably due to a decrease in the net movement of fluid across the pulmonary epithelium.

Acid-Base Equilibrium↗