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Biomedical subjects

J B Hook

Publications and source records attributed to J B Hook.

At least 181 records · Page 10Linked to original sources
PubMed1976

Biochemical and ultrastructural correlates of substrate stimulation of renal organic anion transport.

Penicillin pretreatment enhanced the rate of PAH uptake into separated proximal tubules (collagenase digestion) from 2-week New Zealand white rabbits. A double reciprocal plot of these data suggests that penicillin increases the maximal velocity of PAH uptake. Na, K-ATPase was less in adult tissue but was unaffected by penicillin. No ultrastructural changes could be attributed to the treatment. Thus substrate stimulation of PAH transport does not involve Na, K-ATPase and probably involves soluble, rather than structural proteins.

Adenosine Triphosphatases↗
PubMed1976

Prostaglandin E2 production by renomedullary tissue of DOCA, Goldblatt and spontaneously hypertensive rats.

The realtionship between in vitro prostaglandin production by renal medullary tissue and hypertension was investigated in three models of hypertensive rat, i.e., DOCA, Goldblatt and SHR. Medullary minces were incubated for 30 minutes. Following incubation tissue PGE2 concentration was quantified using mass fragmentography. Media PGE2 concentrations were quantified using radioimmunoassay. Concentrations of PGE2 in tissue from Goldblatts and SHRs were significantly less than normotensive controls. The concentration of PGE2 in media after incubating SHR tissue was significantly less than normotensives. The data suggest that alterations in PGE2 metabolism are similar in Goldblatt and SHR hypertension.

Animals↗
PubMed1976

Effect of furosemide on renal hilar lymph flow.

Furosemide is known to increase total renal blood flow. The purpose of this study was to determine the relationship between this hemodynamic change and renal hilar lymph flow. Renal blood flow was measured with an electromagnetic flowmeter placed on the left renal artery of anesthetized dogs. Lymph was collected from a cannulated hilar vessel. Urine volume loss was not replaced. In the first 10 min after furosemide (1 mg/kg i.v.), lymph flow was significantly increased and then declined toward control within 30 to 40 min. The decline in lymph flow lagged behind the decline in blood flow by about 10 min. In 11 experiments in which there was a significant increase in renal blood flow, renal hilar lymph flow also increased. In 5 experiments in which renal blood flow did not increase after furosemide, lymph flow also did not increase. In both groups, urine volume was significantly increased but the diuresis was less in the group in which renal blood flow and lymph did not increase. When hydrochlorothiazide (5 mg/kg, i.v.) was administered, neither renal blood flow nor hilar lymph flow was altered. The effect of equi-diuretic doses of furosemide and hydrochlorothiazide on renal tissue water content were compared. The amount of water present after furosemide was significantly greater than the amount present after hydrochlorothiazide. These data support the concept that changes in renal hilar lymph flow are more a consequence of changes in renal blood flow than in urine volume.

Animals↗
PubMed1976

Investigations on metabolic modulation of p-aminohippurate accumulation by rabbit renal cortical slices.

Preparation and incubation of renal cortical slices from adult, female, New Zealand white rabbit depleted tissue citrate concentration. Acetate (10.0 mM) in the incubation significantly increased slice citrate concentration and p-aminohippurate (PAH) accumulation. Physiological concentrations of citrate increased PAH accumulation and final medium pH. increasing concentrations of citrate produced a biphasic effect on PAH accumulation. These data suggested that citrate may act as an intracellular modulator of organic anion transport. This hypothesis was tested with other stimulators of PAH accumulation. Physiological concentrations of alpha-ketoglutarate or succinate increased slice accumulation of PAH. Higher concentrations of either substrate significantly inhibited PAH accumulation. Final medium pH increased with increased medium concentration of both substrates. alpha-Ketoglutarate (0.5 mM) increased PAH accumulation but had no effect on slice citrate concentration. Glucose did not alter either PAH accumulation or slice citrate concentration. Slices incubated without substrate were depleted of citrate but not of alpha-ketoglutarate. Acetate (1.0 mM) significantly increased slice concentration of both alpha-ketoglutarate and citrate. These data suggested that organic anion transport could be modulated by several metabolic intermediates acting through similar but separate mechanisms.

Acetates↗
PubMed1976

Natriuretic effect of furosemide after inhibition of prostaglandin synthetase.

The effects of furosemide on stimulation of renin secretion and urinary sodium excretion were studied in dogs pretreated with the prostaglandin synthetase inhibitors, indomethacin and meclofenamate. Pretreatment with these drugs failed to modify the natriuretic response to furosemide but completely blocked the rise in arterial plasma renin concentration produced by the diuretic. The organic acid probenecid did not affect either the natriuretic response or the increase in renin. In separate experiments, it was not possible to separate the effects of indomethacin on prostaglandin secretion, the renin-angiotensin system or renal hemodynamics. It is concluded that in the dog the natriuretic response to furosemide is not linked to the possible prostaglandin-induced increase in renal blood flow. Indomethacin apparently affects furosemide-induced renin secretion at both the vascular and macula densa sites. The data also suggest that the prostaglandins may be more important than the renin-angiotensin system in the modulation of intrarenal hemodynamics.

Animals↗
PubMed1976

Maturation of renal organic acid transport in vivo: substrate stimulation by penicillin.

These experiments were designed to demonstrate that pretreatment of newborn dogs with penicillin will enhance maturation of the renal organic anion transport system in vivo. Littermate pups were injected with procaine penicillin G (300,000 I.U./kg b.i.d. for 3 days) or saline before 2 weeks of age. Animals were surgically prepared on day 16 or 17. Transport of p-aminhippurate (PAH), as an indicator of renal organic anion transport, was quantified by the following procedures: 1) disappearance of a bolus injection from the plasma, 2) renal extraction and 3) rate of secretion in steady-state clearance experiments. The renal handling of insulin was measured simultaneously in all procedures for comparison. Penicillin-treated animals excreted a single intravenous bolus of PAH more rapidly than control animals, with the T1/2 decreased and the constant of elimination (Ke) increased. The extraction of PAH by kidneys of penicillin-treated animals was 165% that of controls. Similarly, the tubular secretion of PAH was increased in treated pups. These data confirm that in newborn animals the renal handling of organic anions in vivo is enhanced by pretreatment with a substrate of the secretory system.

Aminohippuric Acids↗
PubMed1975

Disappearance of p-aminohippurate and inulin from plasma of newborn and adult rats.

The ability of newborn and adult rats to eliminate p-aminohippuric acid and inulin from plasma was determined. The pattern of development is similar to that observed in vitro using renal cortical slices. The fact that function increases to a peak and then declines over the developmental period while organ weight and histology mature progressively suggests a divergence of functional and antomical maturation. Inulin elimination, unlike PAH, increased over the ages tested, and is apparently more closely related to organ growth.

Age Factors↗
PubMed1975

Control of renin secretion in the dog. Effects of furosemide on the vascular and macula densa receptors.

Experiments were undertaken to investigate further the effect of furosemide on renin secretion in the anesthetized dog. To separate the effects of the macula densa and the baroreceptor mechanisms, experiments were conducted in kidneys made nonfiltering by combining 2.5 hours of renal ischemia with ureteral ligation. Furosemide, in a dose of 5 mg/kg, increased renin secretion and decreased renal resistance in dogs with a nonfiltering kidney. Prior dilation of the nonfiltering kidney with either acetylcholine or papaverine prevented changes in both resistance and renin secretion. However, following dilation of the intact filtering kidney with acetylcholine, furosemide caused an increase in renin secretion. Infusion of d,l-propranolol decreased renin secretion in both the filtering and the nonfiltering kidneys. Following propranolol treatment, furosemide increased renin secretion in the filtering kidney but had no effect on renal resistance. These experiments indicate that furosemide stimulates renin secretion by both the macula densa and the baroreceptor mechanisms. The data suggest that stimulation of the sympathetic nervous system may alter renin secretion by modulating the renal baroreceptor, but sympathetic innervation does not appear to be involved in the macula densa mechanism.

Acetylcholine↗
PubMed1975

Effects of indomethacin on furosemide-induced changes in renal blood flow.

The effects of indomethacin on furosemide induced changes in renal blood flow were determined in dogs. Furosemide alone caused an increase in total renal blood flow while indomethacin alone decreased renal blood flow. When furosemide was administered to animals pretreated with indomethacin the increase in renal blood flow was blocked. Changes in intrarenal blood flow distribution were also measured using radioactive microspheres. The pattern of blood flow distribution after furosemide was modified in some of the animals pretreated with indomethacin. Stimulation of renin secretion occurred after furosemide in indomethacin-treated animals. The data suggest that the changes in renal blood flow produced by furosemide may be modulated by the prostaglandin system.

Animals↗
PubMed1975

Substrate stimulation of para-aminohippuric acid transport: effect on uptake and runout.

The ability of penicillin pretreatment to increase PAH accumulation by slices of newborn rabbit renal cortex was dissected into two components, uptake and runout. The oxygen-requiring component of the uptake process was significantly enhanced by penicillin treatment, whereas runout was unaffected. Kinetically, the data suggest that penicillin alters the affinity of the transport system for PAH. Due to the limitations of such a kinetic analysis, no conclusions may be drawn from such a suggestion. However, it may be concluded that penicillin pretreatment increases renal accumulation of PAH solely by stimulating the uptake process. Elucidation of the molecular changes involved will require techniques more sophisticated than uptake into renal cortical slices.

Age Factors↗
PubMed1975

Pharmacodynamic analysis of substrate stimulation of p-aminohippurate transport by newborn rabbit kidney.

Penicillin pretreatment of 2-week-old New Zealand White rabbits significantly increased the ability of renal cortical slices to transport p-aminohippuric acid (PAH). The PAH slice/medium ratio increased with dose to a maximum at 90,000 I.U. of procaine penicillin G. Sodium penicillin G (180,000 I.U.) produced no greater increase. Stimulation was maximal after four penicillin injections at 12-hour intervals. The maximal response was observed 24 hours after the final injection, whereas after 72 hours the capacity of slices from treated animals to transport PAH was no different than control. To determine the effect of a maximal substrate challenge on the development of transport capacity, pregnant does were treated with 90,000 I.U. of procaine penicillin i.m. twice daily through the last half of gestation. Young animals received four penicillin injections before sacrifice. The PAH slice/medium ratio from pups 3 days, 1 and 2 weeks old were not significantly different from that normally observed at 4 weeks. Animals 4 weeks old did not respond to penicillin treatment. Thus, intrinsic transport capacity for PAH is mature at 4 weeks of age. Only before this age may transport be enhanced by substrate. Maximal enhancement of PAH transport capacity occurs when four injections of 90,000 I.U. of procaine penicillin G are administered at 12-hour intervals followed by sacrifice 24 hours after the final injection.

Aging↗