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Biomedical subjects

S K Hong

Publications and source records attributed to S K Hong.

At least 199 records · Page 11Linked to original sources

Effects of SCN- and NO3- on organic anion transport in rabbit kidney cortical slices.

1. The effects of replacement of Cl- by either SCN- or NO3- on the accumulation of p-aminohippurate, the efflux of pre-accumulated p-amino-hippurate and kinetics of p-aminohippurate uptake were investigated in the rabbit kidney cortical slice. 2. The total replacement of Cl- in the incubation medium with SCN- decreased the 60-min slice-to-medium concentration ratio (S/M) of p-amino-hippurate by 75% and that with NO3- by 40%. 3. The decrease in p-aminohippurate accumulation by the inorganic ions was found to be specific for organic anion transport since the uptake of the organic cation, tetraethylammonium, was not influenced by inorganic ions. 4. The influence of NO3- on p-aminohippurate uptake was fully reversible: however, the effect of SCN- could only be partially reversed. 5. Both SCN- and NO3- significantly increased the Km value but had no significant effect on the V value of the p-aminohippurate uptake process. 6. These findings suggest that both SCN- and NO3- are competitive inhibitors of p-aminohippurate transport and, also, that SCN- appears to bind to a membrane component involved in the transport of p-aminohippurate.

Aminohippuric Acids↗

Effect of DIDS on renal tubular transport.

Two stilbene derivates that had been used to covalently label the Cl- carrier in the erythrocyte were investigated for reactivity with the renal organic anion system. These compounds, 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS) and (4,4'-diisothiocyano)-dihydrostilbene-2,2'-disulfonate (H2DIDS), were found to be potent inhibitors (Ki congruent to 35 microM) of p-aminohippurate (PAH) transport in the renal cortical slice without affecting tetraethylammonium (TEA) transport or tissue viability. During renal clearance studies performed in the perfused kidney, DIDS decreased the PAH/inulin clearance ratio to congruent to 1. When the possible renal transport of [3H]H2DIDS was investigated, the renal slice transport or binding of [3H]H2DIDS reached a slice-to-medium ratio of congruent to 6, and this accumulation was decreased by probenecid. In perfused kidney experiments, the [3H]H2DIDS/inulin clearance ratio was congruent to 0.8. Since probenecid reduced this clearance ratio to congruent to 0.5, there was the possibility that H2DIDS underwent tubular secretion. In conclusion, DIDS and H2DIDS interacted with the renal organic anion transport system, which indicated that these compounds were possible probes for this transport system.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

The effect of bis(p-chlorophenyl) acetic acid on the renal function of the rat.

The principle water-soluble metabolite of DDT in mammals has been shown to be DDA (bis(p-chlorophenyl)acetic acid). Previous studies suggested that DDA was secreted by the renal proximal tubule and was reabsorbed at an unspecified site in the nephron. Since DDA has been known to produce alterations in cellular functions, the present study examined the possibility that the renal transport of DDA was capable of causing acute nephrotoxicity. When 100 mg/kg of DDA was infused iv into the rat during a 90 min period, there was a significant decrease (congruent to 20%) in the glomerular filtration rate (GFR) after 110 min from the start of administration. During these experiments, there was no change in the mean arterial blood pressure (MABP), urine flow rate (V), renal clearance of tetraethylammonium (CTEA) or fractional reabsorption of Na (FRNa). After 200 mg/kg of DDA was infused iv into the rat during a 90 min period, there was a 60% decrease in the GFR, CTEA and V. However, the decrease in renal function was accompanied by a dramatic reduction in MABP (125 to 60 mmHg). To determine whether DDA could have produced acute renal failure when the perfusion pressure was kept constant, isolated kidney experiments were performed. In these experiments, DDA (1.0 mM) was present in a dextran perfusate and the perfusion pressure was kept constant at 90 mmHg. During these experiments, the GFR, V and FRNa were decreased significantly. The results indicated that a high perfusate concentration of DDA caused acute renal failure in the isolated kidney which was produced even when the perfusion pressure was kept constant. In conclusion, DDA produced renal failure in vivo which was associated with a reduction in renal perfusion pressure; however, perfused kidney experiments indicated that DDA could have caused a direct effect on nephron function.

Animals↗

Antidiuresis and inhibition of PGE2 excretion by hyperoxia in the conscious dog.

Experiments were performed to determine the influence of varying inspired oxygen tension on renal prostaglandin E2 (PGE2) excretion, renal hemodynamics, and water and electrolyte excretion in the conscious dog. Hypoxic exposure (PIO2 = 56 torr) resulted in a 13% increase in renal blood flow (RBF), while hyperoxic breathing with PIO2 of 700, 1426, or 2139 torr, all resulted in significant 5--7% decline in RBF, a response that was significantly attenuated compared to the striking renal vasoconstriction caused by hyperoxia in anesthetized dogs. Hyperbaric oxygenation (HBO) (1426 torr O2, 2139 torr O2) was associated with unexpected decreases in urine flow (V) of 61% and 70%, respectively. The antidiuresis and mild hemodynamic adjustments were correlated with a 67% decline in urinary PGE2 excretion (UPGE2 x V) when the dogs breathed 700 torr O2, while exposure to 1426 torr O2 and 2139 torr O2 diminished UPGE2 x V by 92% and 99%, respectively. Plasma antidiuretic hormone (ADH) concentration, measured during exposure to 1426 torr O2, was unchanged. In addition, this nonpharmacologic hyperbaric decline in PGE2 excretion was not associated with any changes in sodium excretion of renin secretion, in contrast to the usual depression of these variables with pharmacologic PG inhibition (indomethacin). The HBO antidiuresis may be a consequence of an increased medullary osmotic gradient secondary to reduced vasa recta blood flow. Alternatively, this antiduresis could occur as a consequence of a lowering of the normal functional antagonism existing between PGE2 and ADH, such that the influence of endogenous ADH is potentiated.

Animals↗

Descending influences on the responses of spinocervical tract neurones to chemical stimulation of fine muscle afferents.

1. In cats, extracellular micro-electrode recordings were made from axons of the spinocervical tract (s.c.t.) in both the decerebrate state and during cold block of the spinal cord (reversible spinal state) to examine the effects of intra-arterial injection of algesic agents (bradykinin, potassium, 5-hydroxytryptamine) into the gastrocnemius-soleus (g.s.) muscle on the discharge behaviour of s.c.t. neurones.2. In the decerebrate state without cooling the spinal cord 13% of the cells (eleven out of eighty-three) responded to intra-arterial injection of bradykinin, 33% (twenty-two out of sixty-nine) to 5-hydroxytryptamine, and 38% (thirty-five out of ninety-one) to potassium injection.3. The general time course and the latency of the responses of s.c.t. cells induced by injection of pain-producing substances into the g.s. muscle reflect in many respects the activations of g.s. group III and group IV primary afferent units studied previously.4. For twenty-seven s.c.t. neurones the period of recording was long enough to record the responses of the same cell to injections of algesic agents in both the decerebrate and the reversible spinal state. In the reversible spinal state 83% (nineteen out of twenty-three) of the s.c.t. neurones tested with all the three substances responded to at least one of the algesic agents. In the decerebrate state the percentage was lower (39%).5. Reversible spinalization led not only to a significant increase in the number of s.c.t. neurones responding to the algesic agents used but also to an increase in the magnitude of the chemically induced responses.6. The mean latency of the responses of neurones that were activated in both preparations were shorter in the reversible spinal state than in the decerebrate state.7. Control experiments showed that the responses to bradykinin and potassium were entirely due to the nervous outflow from the g.s. muscle. In contrast, intra-arterially applied 5-hydroxytryptamine influenced the s.c.t. cells via unknown additional sites of action.8. The results indicate that muscular group III and/or group IV units excitable by algesic substances do project on to neurones of the spinocervical tract. Furthermore it is concluded that the responses of s.c.t. neurones to activation of fine muscle afferents by algesic agents are subject to a descending control similar to the well known descending modulation of their responsiveness to cutaneous input. Therefore, in addition to serving as a cutaneous pathway the spinocervical tract may take part in muscular nociception.

Action Potentials↗

Relationship between PAH transport and Na-K-ATPase activity in the rabbit kidney.

The relationship between Na-K-ATPase activity and p-aminohippurate (PAH) transport was examined in renal cortical slices of mixed-breed rabbits by using ouabain to vary the level of Na-K-ATPase activity. Ouabain increased passive PAH uptake, measured in the presence of probenecid. Slice homogenate Na-K-ATPase activity was inhibited by 50% with about 2 X 10(-6) M ouabain. When the concentration was 10(-5) M or above, active PAH uptake was inhibited. Lower concentrations (10(-7) and 10(-6) M) of ouabain stimulated active PAH uptake. Acetate stimulated PAH uptake when medium ouabain was less than 10(-4) M. Ouabain, 10(-5) M and higher, caused intracellular K+ to fall and Na+ to rise. The changes in active PAH uptake observed with ouabain correlated much better with changes in intracellular K+ or Na+ levels (P less than 0.01) than with changes in slice homogenate Na-K-ATPase activity. Vmax for active PAH uptake decreased with 5 X 10(-5) M ouabain, and tended to increase with 10(-7) M ouabain. Ouabain did not alter Km for active PAH uptake. The data support the hypothesis that there is a functional link between active PAH transport and Na-K-ATPase activity. This linkage may be an indirect one mediated by changes in intracellular cation concentrations.

Aminohippuric Acids↗

Urinary excretion of water and electrolytes during open-sea saturation diving to 850 fsw.

The dive was carried out in the open sea to a depth of 850 fsw (26.7 ATA) for 6 days (DD 1--6) in the saturated mode, with personnel transfer capsule (PTC) excursions between 0 and 150 fsw and diver excursions between 0 and 50 fsw from the saturation base. Each diver had two excursion dives on alternate days. Although each PTC excursion lasted approximately 7 h, the actual time spent in the water averaged 10.5 min per diver. For 12 divers, daily excretion of water, electrolytes, aldosterone, and antidiuretic hormone (ADH) was studied, along with plasma composition (including prolactin), before, during, and after hyperbaric exposure. A significant increase in urine flow was observed on DD2--4 (1604 ml/day predive vs. 2300 ml/day on DD 4; P less than 0.05), after which the degree of diuresis decreased to about 1800 ml/day. Urine osmolality changed inversely with urine flow, with the lowest value of 532 mOsm/kg on DD 4. During the postdive period, both urine flow and urine osmolality returned to the predive level. The endogenous creatinine clearance was maintained at about 200 liters/day throughout the dive. The fractional excretion of Na+ remained unchanged while that of K+ increased significantly during hyperbaric exposure, thus decreasing the urinary Na+/K+ ratio. The fractional excretion of total osmotic substances showed a small hyperbaric exposure. Body weight decreased progressively during the initial 4 days of pressure exposure, equalling 2.6 kg on DD 4. These findings suggest that the observed diuresis may be accompanied by a net loss of body water. Neither the plasma prolactin level nor urinary excretion of aldosterone and ADHshowed any consistent change throughout the dive. It thus appears that, although there is a small osmotic component, the observed diuresis is primarily due to the ADH-independent inhibition of fre water reabsorption from the collecting duct by means of a mechanism yet to be identified.

Adult↗

Projections of primary afferent fibres from muscle to neurones of the spinocervical tract of the cat.

1. Micro-electrode recordings were made from axons in the spinocervical tract of decerebrate-spinal cats. 2. The effect of electrical stimulation of afferent fibres in muscle nerves was examined. 3. Stimulation of group III fibres in muscle nerves excited hair only and hair and pressure units in the spinocervical tract. Hair and pressure units also responded to electrical stimulation of group IV fibres. 4. Units of the spinocervical tract excited by stimulation of muscle nerves had receptive fields in the skin overlying the relevant muscles. 5. Stimulation of group III fibres in muscle nerves produced long lasting inhibition of spinocervical tract units. In two such units the inhibitory action of afferent myelinated fibres was enhanced by increasing the stimulus strength so that group IV fibres were recruited.

Animals↗

Effect of SITS on organic anion transport in the rabbit kidney cortical slice.

The effect of SITS (4-acetamido-4'-isothiocyano-2,2'-disulfonic stilbene) on the transport of organic ions in the rabbit kidney cortical slice was studied. SITS at a concentration of 10(-4) to 10(-3) M significantly decreased the slice-to-medium (S/M) concentration ratio of the organic anions p-aminohippurate (PAH), and 2,4,5-trichlorophenoxyacetate, but had no significant effect on that of the organic cation tetraethylammonium. The S/M ratio of PAH decreased to 0.52 +/- 0.03 (SE) in the presence of 10(-3) M SITS. The inhibition of PAH uptake caused by SITS was reversed in the presence of 0.5% bovine serum albumin in the medium. SITS at a concentration of 10(-4) M had no significant effect on the efflux of PAH. However, there was a small increase in PAH efflux at a concentration of 10(-3) M SITS. A Lineweaver-Burk analysis of the data indicates that SITS competitively inhibits PAH uptake and that SITS has a Ki value of 2.3 X 10(-4) M. SITS had no effect on the tissue water content, [14C]inulin space, or intracellular Na and K concentrations. It is suggested that the primary effect of SITS is to inhibit the entry of organic anions from the medium into the cell across the basolateral membrane.

2,4,5-Trichlorophenoxyacetic Acid↗

Physiological responses to head-out immersion in water at 11 ATA.

Cardiorespiratory, thermal, and renal responses to a 30-min head-out immersion in 15 degree C water were studied at 1-ATA air and 11-ATA helium-oxygne environments in four male subjects wearing dry suits. Cardiorespiratory responses to immersion (reductions in heart rate, expiratory reserve volume, vital capacity, and thoracic impedance; and increases in stroke volume, cardiac output, and inspiratory capacity) were comparable at both pressures. However, thermal responses to immersion (a reduction in mean skin temperature and increases in skin heat flux and suit conductance) were significantly greater at 11 ATA compared to those at 1 ATA. The rate of urinary excretion of norepinephrine increased significantly during and after immersion at 11 ATA but not at 1 ATA. In contrast, the urinary excretion of epinephrine was not altered by pressure or immersion. The immersion diuresis was greater and lasted longer at 11 ATA than at 1 ATA although there was no difference in the endogenous creatinine excretion . This diuresis was accompanied by a significant natriuresis which was more marked at 1 ATA than at 11 ATA. At 1 ATA, the urinary excretion of both aldosterone and antidiuretic hormone (ADH) decreased during immersion. At 11 ATA, the rate of excretion of these hormones before immersion was lower compared to that at 1 ATA and did not change significantly during immersion. These results indicate that immersion in a hyperbaric helium-oxygen environment presents a greater cold stress than at 1-ATA air, and also that immersion diuresis and natriuresis at high pressure may be induced by a factor other than inhibition of aldosterone and ADH.

Adult↗

Heart rate response to breath holding at 18.6 ATA.

The heart rate (HR) responses to breath-holding (BH) with the without face immersion (FI) in 31 or 27 degrees C water was studied in 1 ATA air and hyperbaric He-O2 environments in 4 male subjects during a dry saturation dive to simulated depth of 580 ft (18.6 ATA). When a 60 sec BH or FI was performed while leaning forward, there was a significant linear correlation between the maximal bradycardial response (delta HRmax) and ambient pressure for simple BH (r-0.08, P less than 0.05) and 31 degrees C FI (r = 0.91, P less than 0.01), but not for 27 degrees C FI. A similar trend was seen during 30 sec BH's while seated erect. The facial cold-dependent component of the FI bradycardia was not significantly altered by pressure. In general, there were significant correlations between the initial HR and the initial thoracic conductive volume (TCV; measured by the four-electrode Minnesota impedance cardiograph), and between the initial TCV and delta HRmax observed during seated erect BH's. Since the TCV was generally higher at depth, it is suggested that a mechanical effect due to increased TCV at depth, possibly related to increased gas density, is at least partly responsible for the pressure dependence of BH bradycardia.

Atmospheric Pressure↗