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Biomedical subjects

A D Baines

Publications and source records attributed to A D Baines.

At least 55 records · Page 3Linked to original sources
PubMed1984

Gluconeogenesis and phosphate reabsorption in isolated lactate- or pyruvate-perfused rat kidneys.

Recent experiments suggest that cytoplasmic free NAD inhibits renal phosphate reabsorption and that gluconeogenesis, by increasing NAD concentration, inhibits phosphate reabsorption. To examine these relationships further we measured phosphate reabsorption by isolated kidneys perfused with either lactate or pyruvate. Lactate perfusion increased the ratio of the cytoplasmic redox couple (glycerol-3-phosphate/dihydroxyacetone phosphate) in snap-frozen kidneys 3-fold relative to the ratio with pyruvate perfusion (p less than 0.001). Inulin clearance and fractional phosphate reabsorption were lower with lactate than with pyruvate perfusion. Phosphate reabsorption decreased throughout the lactate perfusion but was constant for 1 h of pyruvate perfusion. Basal and norepinephrine (NE)-stimulated gluconeogenesis were lower with lactate than with pyruvate perfusion. With lactate and pyruvate perfusions, NE induced equal increases in fractional sodium reabsorption, although only with pyruvate perfusion was there increased phosphate reabsorption. In these experiments, oxidative phosphorylation, not cytoplasmic free NAD concentrations, influenced phosphate reabsorption, and NE-stimulated gluconeogenesis was associated with increased phosphate reabsorption.

Absorption↗
PubMed1983

Nervous disorders of renal function.

Renal nerves contribute to the genesis of at least four disease processes. 1. Excess renal nerve activity contributes significantly to salt and water retention by patients with congestive circulatory failure. 2. Circumstantial evidence suggests that dopamine production may be deficient in a group of patients with idiopathic edema. Aldosterone secretion is high in this group and it has been shown that dopamine exerts a tonic inhibitory effect on angiotensin-stimulated aldosterone secretion. 3. Excess renal nerve activity probably plays a crucial role in the transition from hypotension and pre-renal failure to ischemic acute tubular necrosis. 4. Without doubt hyperactivity of renal nerves causes systemic hypertension in a variety of animal disease models. There is also good reason to believe that this occurs in some forms of human hypertension. The effects of the sympathetic nervous system on renal vascular resistance, renin release, tubular electrolyte reabsorption and aldosterone secretion are discussed in the context of these four diseases.

Acute Kidney Injury↗
PubMed1983

Natriuretic effect of atrial extract on isolated perfused rat kidney.

To examine the mechanisms underlying the natriuretic action of a partially purified extract of rat atria (AE) we injected the equivalent of one atrium into isolated perfused rat kidneys. Some kidneys received an infusion of angiotensin II at 0.5 ng/min throughout the experiment. In the absence of angiotensin AE had a variable effect on renal vascular resistance (RVR) but, in the presence of angiotensin II, AE consistently decreased RVR by 3% for 5 min followed by a slight increase. Inulin clearance and filtration fraction increased slightly but significantly. AE increased sodium, chloride, phosphate, and free water clearance but not potassium excretion. Ventricular extract had no effect on any of these variables. Furosemide (50-250 micrograms) increased sodium, chloride, and potassium but not phosphate or free water excretion. AE did not alter dopamine or norepinephrine excretion. We conclude that AE increases the glomerular filtration rate (GFR) and inhibits tubular reabsorption by mechanisms which differ, at least in part, from those affected by furosemide.

Animals↗
PubMed1983

Suppression of basal and stimulated noradrenergic activities by the dopamine agonist bromocriptine in man.

This study was designed to determine the effects of dopaminergic receptor stimulation on basal and stimulated catecholamine release in man. Five normal white male volunteer subjects were studied in metabolic balance at constant 150-meq sodium, 60-meq potassium intake and then daily for 8 days on an isocaloric constant diet of 10 meq sodium and 60 meq potassium/day in each of two separate protocols. In one protocol, the subjects received the dopamine agonist bromocriptine for 14 days before and during the study; in the other protocol, placebo was substituted for bromocriptine. During normal sodium intake, bromocriptine suppressed supine plasma norepinephrine concentrations from 193 +/- 10 to 159 +/- 9 pg/ml (P = 0.01). Dietary sodium depletion increased supine plasma norepinephrine concentrations in subjects taking placebo from 193 +/- 10 to 229 +/- 10 pg/ml (P less than 0.001). Bromocriptine prevented the supine plasma norepinephrine response to sodium depletion. After discontinuation of bromocriptine treatment, supine plasma norepinephrine concentrations returned to placebo control values. Upright posture stimulated an increase in plasma norepinephrine concentrations from 193 +/- 10 to 419 +/- 30 pg/ml (P = 0.0001) during normal sodium intake, and bromocriptine suppressed this response from 419 +/- 30 to 286 +/- 29 pg/ml (P = 0.004). Dietary sodium depletion enhanced the plasma norepinephrine response to upright posture, and bromocriptine markedly suppressed this enhancement. After discontinuation of bromocriptine treatment, supine and upright plasma norepinephrine concentrations returned to placebo control values. Bromocriptine induced a parallel downward shift in the inverse hyperbolic relationship between the plasma norepinephrine concentration and urinary sodium excretion in erect subjects, and decreased overnight urinary norepinephrine excretion in supine subjects from 1.1 +/- 0.1 to 0.6 +/- 0.1 ng/h (P = 0.0002). No consistent effects of bromocriptine on plasma epinephrine or dopamine concentrations were observed. The results of this study strongly suggest an inhibitory action of dopamine receptor stimulation by bromocriptine on basal and stimulated norepinephrine output at noradrenergic nerve terminals in the central nervous system and/or the periphery.

Adult↗
PubMed1982

Effects of salt intake and renal denervation on catecholamine catabolism and excretion.

My study was designed to measure the effect of salt intake on secretion and catabolism of catecholamines by the kidney and renal nerve contributions to urinary catecholamine excretion. Rats with one chronically denervated (DEN) and one innervated (INN) kidney were fed either high salt (HS) or low salt (LS) diets for 5 to 14 days. Under Inactin anesthesia rats were expanded with isotonic saline while LS rats received 10% mannitol to produce the same urine flow rates. Epinephrine excretion was ten times greater from LS than from HS rats; however, epinephrine/inulin excretion was the same from INN and DEN kidneys. Norepinephrine/inulin excretion was 30% less from DEN than from INN kidneys in both HS and LS rats (P less than 0.01). Dopamine/inulin excretion was 20% less from the DEN kidney than from the INN kidney of HS rats (P less than 0.05), but the 5% lower dopamine/inulin excretion from DEN than from INN of LS rats was not significant. Norepinephrine and dopamine tubular secretions from the rats, estimated by microinjecting radioactive tracers beneath the renal capsule, were 21 and 65%, respectively. After the microinjection, 68% of radioactive norepinephrine and 65% of radioactive dopamine were secreted unchanged. Catecholamine secretion rates and catabolism were not altered by denervation or different salt intakes. Estimated neural NE release was 1 ng/min in INN kidneys of both HS and LS rats; dopamine release 0.6 ng/min in kidneys of HS rats. Thus, when anesthesized, renal nerves contribute 30% to urinary NE and up to 21% to urinary dopamine excretion. Salt intake did not influence NE release from renal nerves or catecholamine secretion and catabolism by the kidney, but salt depletion decreased the renal nerve contribution to urinary dopamine excretion.

Animals↗
PubMed1982

Neural and extraneural catecholamine production by rat kidneys.

Catecholamine production by innervated kidneys was examined by radioenzymatic assay of norepinephrine (NE), epinephrine (E), and dopamine (DA) in lymph, urine, arterial plasma, and renal venous plasma of hydropenic rats. Denervation reduced NE excretion in urine by 18% and both NE and DA efflux in renal venous plasma by 37 and 30%, respectively. The kidney's handling of E was unaltered by denervation. Renal nerves added 1.0 +/- 0.2 ng/min to the efflux of NE in urine and renal venous plasma. Denervation reduced this efflux to -0.1 +/- 0.2 ng/min. DA efflux from innervated kidneys was 1.4 +/- 0.2 ng/min but only half came from renal nerves, as denervated kidneys released 0.7 +/- 0.1 ng/min. Renal lymph from innervated kidneys contained slightly more NE but less DA than arterial plasma. We conclude that renal nerves release both NE and DA but that half of the renal contribution to urine and renal venous plasma DA efflux comes from extraneuronal tissue. Renal lymph NE and DA concentrations are similar to those in arterial plasma, suggesting that peritubular concentrations are low everywhere except within renal clefts.

Animals↗
PubMed1982

Nonoxidative glucose metabolism a prerequisite for formation of dilute urine.

To examine links between norepinephrine- (NE) stimulated sodium transport and gluconeogenesis, we perfused isolated rat kidneys with 6% albumin, containing various combinations of glucose, alanine, pyruvate. and lactate and inhibitors of gluconeogenesis (0.1 mM mercaptopicolinate, MP) or glucose metabolism (0.2-0.5 mM 2-deoxyglucose, DG). Inulin clearance, fractional potassium reabsorption, total sodium reabsorption, and free water clearance were higher in kidneys perfused with 5 mM glucose plus 2 mM alanine than in kidneys perfused with either 10 mM lactate or 5 mM pyruvate. NE, added after 40 min of perfusion, decreased fractional sodium and potassium excretion in all experiments. In lactate- and/or pyruvate-perfused kidneys NE decreased fractional water excretion with little increase in free water clearance; free water formation was lowest in kidneys perfused with DG or MP. Glucose (5 mM) reversed the inhibitory effect of MP on free water clearance. In glucose-perfused kidneys NE did not decrease fractional water excretion, whereas free water clearance increased threefold. NE stimulated glucose production from pyruvate 2.4-fold and from lactate 1.6-fold. MP inhibited gluconeogenesis both in the basal state and after NE. We conclude that the formation of dilute urine requires nonoxidative glucose metabolism to maintain low water permeability in the diluting segment and a high peritubular glucose concentration that is ensured by gluconeogenesis in adjacent proximal tubules.

Animals↗
PubMed1981

Renal nerves and catecholamine excretion.

To determine which neurotransmitters are released into urine by renal nerves, we either acutely denervated one kidney or stimulated renal nerves by activation of the baroreflex. Acute denervation increased dopamine (DA) and decreased norepinephrine (NE) excretion from the denervated kidney. In contrast, DA excretion decreased and NE excretion increased progressively from the contralateral innervated kidney. Sodium excretion related directly to DA and inversely to NE excretion. In chronic denervation experiments, baroreceptor stimulation increased NE excretion by 25% more from the innervated kidney than from its contralateral denervated mate, while DA excretion increased by 50% only from the innervated kidney. Baroreflex-stimulated NE and DA excretion from innervated kidneys was reduced by prior feeding of a low salt diet. The response was completely abolished by a high salt diet. Sodium excretion increased by the same proportion from innervated and chronically denervated kidneys following baroreceptor stimulation. In conclusion, 1) renal nerves release both NE and DA, 2) after acute unilateral denervation sodium excretion related directly with DA and inversely with NE excretion, and 3) urinary excretion of NE and DA derived from renal nerves was influenced by dietary sodium intake.

Animals↗
PubMed1981

Decreased plasma and urinary dopamine during dietary sodium depletion in man.

This study was designed to investigate the influence of dietary sodium restriction on plasma and urine dopamine levels. Five normal white male volunteer subjects wee studied in metabolic balance at constant 150 meq sodium, 60 meq potassium intake and then daily for 7 days on an isocaloric constant diet of 10 meq sodium and 60 meq potassium/day. With dietary sodium restriction, urinary sodium excretion decreased from 152 +/- 13 meq/day in stepwise fashion to 7 +/- 1 meq/day (P less than 0.001) on day 7. On the first day of dietary sodium restriction, a sodium deficit of 122 meq was associated with a decrease in supine plasma dopamine concentration from 58 +/- 10 to 45 +/- 7 pg/ml (P less than values for 2 days but decreased again to 43 +/- 12 pg/ml (P less than 0.05) on day 4 of sodium restriction and remained significantly lower than control on days 5-7 of sodium restriction (P less than 0.01). Supine plasma norepinephrine concentration increased from 193 +/- 34 to 232 +/- 29 pg/ml (P less than 0.05) on day 1 of sodium restriction and remained elevated during each subsequent day of low sodium intake (P less than 0.001). Supine plasma epinephrine concentration was unchanged by sodium restriction. Urinary dopamine excretion decreased from 12 +/- 2 to 8 +/- 1 microgram/h (P less than 0.05) on day 2 of sodium restriction and remained significantly low during each subsequent day of low sodium intake. Urinary norepinephrine was unchanged by sodium restriction. The data indicate a variable decrease in plasma dopamine concentration and a constant decrease in urinary dopamine excretion during the course of dietary sodium restriction in man.

Adult↗
PubMed1980

Flow through brushborders and similar protuberant wall structures.

Longitudinal flow through channels with protuberant wall structures such as brushborders were studied both experimentally and theoretically. The experiments were performed using tubes with synthetic internal brushborders, scaled to resemble the geometry and flow in proximal tubules of the kidney. Fractional flow rates in the brushborder were deduced from transit times of dye traces through the central core and total flow rate. The measured ratios of brushborder to core flow QB/QC were found to be independent of Reynolds number over the range Re = 0.01 - 0.2. They agreed reasonably well with theoretical predictions based on the Kozeny-Carman equation for flow through arrays of parallel cylinders. The predictions can be extended to arbitrary geometries and turbulent flow conditions by appropriate modifications. Extrapolation of the results to the proximal tubule of the kidney indicate that brushborder flowrates there vary from 0.003 to 0.09% of total flow. Any axial transport in these structures would be predominantly diffusive in nature, and would be highly unlikely to affect radial brushborder gradients and transmural flux.

Animals↗
PubMed1979

Computer simulation of flow-dependent absorption in microperfused short Henle's loop of rats.

With computer simulation we examined the extent to which current theories and experimental data explain function of single microperfused superficial Henle's loops in rats. In the model standard phenomenological equations describe transport; two sets of transport parameters labeled rat and rabbit were taken from published experiments; Michaelis-Menten kinetics in the ascending thick limb were adjusted arbitrarily; tubular radius is either constant or depends on luminal pressure with compliance based on experimental observations; the interstitium is an infinite sink with salt and urea concentrations constant in the cortex and exponentially increasing in the outer medulla; concentrations resemble those found in hydropenic or saline diuretic rats. The following predictions were obtained. The model with rabbit parameters does not recirculate urea and will not operate with high medullary urea concentrations; with rat parameters too much urea recirculates an the results of perfusion with equilibrium solution are not reproduced. Using a compromise between rat and rabbit parameters, the model reproduces water absorption, salt reabsorption, and urea recirculation as observed in vivo in rat loops perfused at 5-40 nl/min. It also simulates perfusion with saline, equilibrium solution, saline plus furosemide, and 300 mM mannitol. When the model includes a short early distal segment, effluent salt concentration reaches a minimum at a 15 nl/min perfusion rate as observed in vivo; however, concentration at the macula densa is a monotonically increasing function of flow. When permeation rate is a function of wall surface area and thickness a better fit to experimental results is produced. However, the effect is small: water absorption alters by 4% or less and effluent salt concentration is reduced by up to 10% at low perfusion rates. Comparison of rigid and compliant loops shows no relationship between transit time per se and reabsorption.

Animals↗
PubMed1979

Effects of lumen volume transit time and pressure on loop of Henle function.

Experiments on Henle's loops were designed to demonstrate the relationships of absorption to distal pressure, transit time, and luminal diameter. Loops of superficial nephrons in hydropenic rats, isolated from the rest of the nephron by oil or solid paraffin blocks, were microperfused at 13.6--20 nl/min. Two samples of fluid were collected from the early distal tubule--one with suction in order to lower distal pressure and reduce luminal volume, the other without suction so that the lumen was distended. Transit times were 30 +/- 2 s without and 19 +/- 2 s with suction. Proximal tubule pressure and perfusion rate were not altered by collection with suction. Absolute absorption, however, descreased from 10.6 +/- 0.4 to 8.4 +/- 0.4 nl/min (P less than 0.001). When salt transport was inhibited by 10(-4) M furosemide in the perfusate, water absorption was 7.8 +/- 0.7 nl/min without suction and 6.1 +/- 0.8 nl/min with suction (P less than 0.01). Computer simulation of Henle's loop shows that these observations cannot be explained by changes in transit time, hydrostatic pressure, or unstirred layers. The observations are simulated when radial fluxes depend on wall thickness and surface area in the descending thin limb.

Animals↗
PubMed1979

Tubular secretion and metabolism of dopamine, norepinephrine, methoxytyramine and normetanephrine by the rat kidney.

The fate of catecholamines released in rat kidneys was examined by microinjecting tritiated norepinephrine (NE), normetanephrine (NMN), dopamine (D) and 3-methoxytyramine (3MT) into proximal and distal tubule lumina and peritubular capillaries. [14C] Inulin included in the injectate served as a reference standard. After injection of NE, D, NMN and 3MT at 0.1 to 4.0 pg/min for 4 to 10 min into proximal tubules, 87 to 94% was recovered in the urine of the injected kidney. Less than 10% of the amines was chemically altered during passage through the nephron. After injection into capillaries, percentages secreted in the first passage through the kidney were: D, 25 +/- 5; 3MT, 47 +/- 3; NE, 13 +/- 2; and NMN, 4 +/- 3. After D capillary injections, excretion of 3MT and D from the microinjected was twice that from the contralateral kidney. Acidic metabolites, homovanillic acid and dihydroxyphenylacetic acid were excreted equally by both kidneys. There was no appreciable difference in the products excreted from left and right kidneys after NE injections. In summary, D released into the peritubular space is converted to 3MT and both compounds are secreted avidly. NE released into the peritubular circulation is converted to NMN and both compounds are secreted but to a much smaller extent than occurs with D and 3MT.

Animals↗
PubMed1978

Examination of transport equations pertaining to permeable elastic tubules such as Henle's loop.

The transport equations applicable to loops of Henle and similar elastic permeable tubules were re-examined to assess the effect of radial transport resistance in the lumen and tubule geometry on solute transport. Active transport at the wall as well as external gradients equivalent to a 2--1,000-fold concentration increase per centimeter of distance were considered. Wall permeabilities and active transport constants were varied up to 2 . 10(-2) cm/s. It is shown that for conditions applicable to the loop of Henle, resistance to radial solute transfer in the lumen is negligible, both for passive and active transmural transport with concomitant water flux, and that axial dispersion further reduces that resistance. These conclusions apply equally to conical and elliptical geometries likely to arise in loop operation. The validity of Poiseuille's equation for these geometries is discussed. Ii is concluded that the one-dimensional transport equations are a valid representation of loop operation.

Biological Transport, Active↗
PubMed1978

Effect of acute blood volume expansion on cardiac output, plasma dopamine beta-hydroxylase, and renal function in rats with chronic constriction of the ascending aorta.

To examine the effect of raised left atrial pressure (AP) on the relationship of cardiac output to renal function, we constricted the ascending aorta in rats (AC) and 1-6 months later tested their response to acute volume expansion (VE) with blood (2% body weight, iv). Sham-operated (SH) rats were controls. In AC rats heart weight increased 38%, but cardiac output was 47% lower. Statistically significant differences in the initial clearance periods were (AC vs. SH): venous pressure (VP) 8 +/- 2 vs. 3+/- 1 cm H2O; inulin clearance (CIN) 0.61 +/- 0.06 vs. 0.84 +/- 0.04 ml/min; sodium excretion (UNAV) 1.2 +/- 0.2 vs. 2.1 +/- 0.3 muequiv./min. Filtration fraction, fractional UNaV, mean arterial pressure (MAP), and plasma dopamine beta-hydroxylase (DBH) were the same in both groups. After VE, cardiac output increased proportionately more in AC (69% vs. 27%); however, the absolute increases were not different. UNaV increased proportionately more in AC rats, but the absolute increase was less (5.1 vs. 7.5 muequiv./min). Multiple variable regression analysis showed that UNaV correlated with CIN, MAP, and VP, with no difference between AC and SH animals. Cardiovascular-renal relationships were indistinguishable from previous descriptions of dogs and rats with chronic vena caval constriction. Modulation of renal function by left AP was not apparent. In both groups after the peak response to VE, UNaV decreased in association with decreased cardiac output and increased sympathetic nervous activity as indicated by raised DBH levels. After VE, VP remained high in AC but not in SH animals.

Animals↗
PubMed1976

Propranolol induces acute natriuresis by beta blockade and dopaminergic stimulation.

dl-Propranolol (0.8-1.6 mg/kg - h for 1 h) produced a transient two- to three-fold increase in sodium excretion in nondiuretic rats infused with Pitressin and aldosterone and in water diuretic rats. Sodium excretion increased more in rats depleted of renin by chronic Doca and salt administration than in rats maintained on a low salt diet. An angiotensin inhibitor (1,sarcosine-8,valine angiotensin II) decreased sodium excretion. Therefore the natriuresis was not mediated by antidiuretic hormone, aldosterone, or renin-angiotensin. d-Propranolol did not produce a natriuresis. Prior treatment with phenoxybenzamine did not prevent the natriuretic response but chlorisondamine pretreatment did. The natriuresis is produced by beta blockade and requires post ganglionic nerve function but is independent of alpha receptors. dl-Propranolol decreased heart rate and cardiac output but systemic pressure did not fall and renal blood flow increased. This suggests a dopamine-mediated renal vasodilation and natriuresis. Haloperidol and pimozide, both dopamine blocking agents with minimal beta blocking effects, prevented the natriuretic response. We conclude that propranolol may increase sodium excretion directly by blocking beta receptors in the distal nephron and indirectly by dopamine-mediated renal vasodilation.

Adrenergic beta-Antagonists↗