bluuebunny/crossref_metadata_2025 huggingface dataset:
Restoration of tubuloglomerular feedback in volume-expanded rats by angiotensin II
Authors: Schnermann J. , Briggs J. P.
Published: December 2017

Experiments were performed in anesthetized rats to examine whether angiotensin II corrects the attenuation of tubuloglomerular feedback (TGF) responses produced by acute extracellular volume expansion. Volume expansion was achieved by an infusion of isotonic saline at a rate of 9 ml/h. When urine flow had stabilized, an increase in loop of Henle flow from 0 to 45 nl/min caused a fall in stop-flow pressure (PSF) by 3.7 +/- 0.3 mmHg and in single-nephron glomerular filtration rate (SNGFR) by 5.1 +/- 1.7 nl/min. During continued saline administration angiotensin II was infused at 16, 48, or 96 ng.kg-1.min-1 while renal arterial pressure was held constant by suprarenal aortic clamping. The mean responses of PSF increased to 5.9 +/- 0.6, 9.8 +/- 0.7, and 14.9 +/- 1.7 mmHg. Angiotensin II infused at 54 ng.kg-1.min-1 increased the SNGFR response to 15.1 +/- 2.1 nl/min, whereas kidney GFR and distal SNGFR fell. Subcapsular pressure was not significantly altered by angiotensin II infusion (16 ng.kg-1.min-1). Plasma angiotensin (y, pg/ml) as a function of angiotensin II infusion rate (x, ng.kg-1.min-1 for approximately 20 min) was found to fit the function y = 2.89 + 3.53x. An infusion of approximately 15 ng.kg-1.min-1 restored plasma angiotensin levels in the volume-expanded rats to hydropenic values. These data confirm that angiotensin II may play a role as a physiological regulator of TGF sensitivity.
Renal responses to lower body negative pressure in humans
Authors: Tidgren B. , Hjemdahl P. , Theodorsson E. , Nussberger J.
Published: December 2017

Renal blood flow, renal sympathetic nerve activity, assessed by the renal overflows of norepinephrine (NE), dopamine (DA), and neuropeptide Y-like immunoreactivity (NPY-LI), as well as plasma renin activity and angiotensin II (ANG II) were evaluated during stepwise increases in lower body negative pressure (LBNP) in 10 healthy volunteers. The fractional extraction of epinephrine (Epi) was used to assess renal catecholamine removal (approximately 50%) from arterial plasma. Renal NE, DA, and NPY-LI overflows at rest were 235 +/- 31, 30 +/- 5, and 0.6 +/- 0.2 pmol/min, respectively. LBNP increased renal vascular resistance (RVR) by 52% and renal NE overflow by 31%. Renin release increased by 330% (from 64 +/- 12 units/min) and arterial ANG II levels by 119%, without altering the renal ANG II extraction (which was approximately 50%). Renal DA and NPY-LI overflows were unaffected. A “;vaso-vagal” reaction in one subject was associated with cessation of renal NE overflow and marked elevations of arterial Epi, renal renin release, and arterial ANG II. Selective unloading of cardiopulmonary baroreceptors by low-level LBNP did not affect RVR, whereas higher levels of LBNP caused renal vasoconstriction probably mediated in part by increased renal sympathetic nerve activity and in part by ANG II.
Relative osmotic effects of raffinose, KCl, and NaCl across basolateral cell membrane
Authors: Welling L. W. , Welling D. J. , Ochs T.
Published: December 2017

Lumen-collapsed segments of rabbit S2 proximal tubule were bathed in isotonic medium and then exposed acutely to a medium made hypertonic by the addition of raffinose, NaCl, KCl, Na gluconate, K gluconate, or choline Cl. The result was a rapid efflux of water and a shrinking of the tubule, which could be measured by video techniques within the first 0.1 s. After reequilibration in isotonic medium, each tubule was then exposed to a second hypertonic medium to provide a direct comparison between two different solutes, either NaCl vs. KCl or raffinose vs. any one of the other solutes. Because raffinose is impermeant across the basolateral cell membrane, the ratio of its effect to that of another solute is a measure of the reflection coefficient (sigma) of that other solute. The following results were obtained: sigma KCl = 0.70 +/- 0.02, sigma K gluconate = 0.97 +/- 0.07, sigma Na gluconate = 0.84 +/- 0.06, and sigma choline Cl = 0.75 +/- 0.06. We previously have reported sigma NaCl = 0.56 +/- 0.07. If sigma of each salt is considered to be the arithmetic average of its component parts, and if gluconate and choline are considered to be impermeant, we also obtain sigma Na+ = 0.68, sigma K+ = 0.94, and sigma Cl- = 0.50.
Effects of growth hormone and IGF-I on renal function in rats with normal and reduced renal mass
Authors: Miller S. B. , Hansen V. A. , Hammerman M. R.
Published: December 2017

To characterize actions of growth hormone (GH) and insulin-like growth factor ( (IGF-I) on renal function in rats with normal and reduced renal mass, we administered recombinant bovine growth hormone (bGH) or human IGF-I (hIGF-I) to normal rats or to rats that had undergone unilateral nephrectomy and two-thirds infarction of the contralateral kidney, and measured inulin and p-aminohippurate clearances over 10-17 days. Administration of either bGH (100-200 micrograms/day) or hIGF-I (200 micrograms/day) to rats with normal renal mass increased inulin and p-aminohippurate clearances compared with those measured in animals that received vehicle. Filtration fractions were not affected by either bGH or hIGF-I. Inulin clearance was decreased to approximately 17% of normal 1 day after reduction of renal mass in rats. Over the next 3 days insulin clearance increased significantly in rats with reduced renal mass that were administered vehicle. No further enhancement occurred during the next 7 days. Neither bGH nor hIGF-I affected inulin clearance in rats with reduced renal mass. We conclude that both GH and IGF-I enhance glomerular filtration rate when administered to rats with normal renal mass, but not when administered in the same quantities to rats in which renal functional mass is reduced. Glomerular filtration rate increases within 4 days of renal mass reduction independent of exogenous GH or IGF-I.
Role of prostaglandins and endothelium-derived relaxing factor on the renal response to acetylcholine
Authors: Salom M. G. , Lahera V. , Romero J. C.
Published: December 2017

Acetylcholine (ACh) stimulates the endothelial release of prostacyclin and endothelium-derived relaxing factor (EDRF). However, the relative participation of these substances in mediating the renal effects of ACh remains undefined. To elucidate this issue, we studied the modifications of renal responses to intra-renal ACh infusion (25 ng.kg-1.min-1) produced by blocking the synthesis of EDRF and/or prostaglandins (PG) in anesthetized dogs. ACh induced a significant increase in renal blood flow (RBF) (34%), urine volume (UV) (450%), and urinary sodium excretion (UNaV)(259%), which remained unaltered after blocking the synthesis of EDRF [NG-monomethyl-L-arginine (LNMMA), 50 micrograms.kg-1.min-1 intrarenal] or PG (meclofenamate, 5 mg/kg iv). However, the simultaneous administration of meclofenamate and LNMMA prevented the ACh-induced increase in RBF and UV but not in UNaV. The concomitant infusion of L-arginine but not D-arginine prevented these blocking effects of LNMMA. It was concluded that the ACh-induced increases in RBF and UV, but not UNaV, are mediated by both PG and EDRF. The hemodynamic and diuretic effect of either one of these mediators can be fully compensated during the blockade of the other.
Ontogeny of renal renin release in spontaneously hypertensive rat and Wistar-Kyoto rat
Authors: Henrich W. L. , Levi M.
Published: December 2017

The role of renin-angiotensin system in generation of genetic hypertension is unclear. Renal renin secretion was examined in renal superficial cortical slices from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) at 4 wk (prehypertensive), 6 wk (early hypertensive), and 12 wk (established hypertension) of age. Basal renin release in SHR was greater at 4 wk (749 +/- 55 vs. 480 +/- 50 ng/mg, P less than 0.005) and at 6 wk (428 +/- 70 vs. 266 +/- 60 ng/mg, P less than 0.02). Basal renin release declined by 43% between 4 and 6 wk and by 34% between 6- and 12-wk time periods in SHR. In SHR and WKY at all ages, renin responses to stimulation with isoproterenol (ISO, 10(-5) and 10(-6) M, respectively) were similar. Angiotensin II (ANG II) resulted in a significant reduction in renin release in both SHR and WKY at 10(-7) M in all age groups. The ANG II-induced percent change in renin release from control of SHR was less compared with WKY rats at 10(-8) and 10(-9)M at 4 wk of age. When ANG II was tested in presence of beta-adrenergic stimulation, a comparable renin inhibitory response was observed in both SHR and WKY. The number of ANG II-binding sites in proximal tubular brush-border membrane (BBM) was increased in SHR vs. WKY rats (458 +/- 18 vs. 235 +/- 12 fmol ANG II/mg BBM protein, P less than 0.001) at 4 wk of age. These data document increased basal renin release and ANG II-binding sites in proximal tubular BBM in 4 wk SHR compared with age-matched WKY rat.(ABSTRACT TRUNCATED AT 250 WORDS)
Renal blood flow response to angiotensin II infusions in conscious pregnant rabbits
Authors: Brown G. P. , Venuto R. C.
Published: December 2017

Renal blood flow (RBF) was measured in conscious rabbits while nonpregnant and during pregnancy using chronically implanted ultrasonic transit-time flow probes. The effects of the cyclooxygenase inhibitor meclofenamate (5 mg/kg) and the angiotensin-converting-enzyme inhibitor captopril (5 mg/kg) on basal RBF and on RBF responses to systemic angiotensin II infusions (2.5-80 ng.kg-1.min-1) were determined. Basal RBF declined (P less than 0.001 to P less than 0.005) with meclofenamate by 9-16% in pregnant (n = 7) and by 10% in nonpregnant (n = 7) rabbits. Captopril increased (P less than 0.05 to P less than 0.01) RBF by 9-11% in pregnant (n = 5) and by 12% in nonpregnant (n = 5) rabbits. There was no effect of the vehicle (normal saline) on RBF. The reduction in RBF (% from baseline) in response to infused angiotensin II was attenuated in pregnant compared with nonpregnant rabbits. Pretreatment with meclofenamate enhanced the renal vasoconstrictor action of angiotensin II in a similar fashion in both pregnant and nonpregnant rabbits. Captopril or saline did not alter the RBF responses to angiotensin II infusions. Mean arterial pressure was lower in pregnant (78 +/- 3 mmHg, n = 7) vs. nonpregnant (88 +/- 5 mmHg, n = 10) rabbits, suggesting lower total peripheral resistance. The data indicate 1) chronically implanted ultrasonic flow probes can be an effective tool for monitoring RBF in conscious rabbits, 2) prostaglandins and the renin-angiotensin system influence basal RBF in conscious rabbits, and 3) the renal vasoconstrictor effect of angiotensin II is blunted in pregnant rabbits and this attenuated response appears to be independent of prostaglandins.
Fluoride mobilizes intracellular calcium and promotes Ca2+ influx in rat proximal tubules
Authors: Dominguez J. H. , Garcia J. G. , Rothrock J. K. , English D. , Mann C.
Published: December 2017

In the renal proximal tubule, external Ca2+ ([Ca2+]o) is required for parathyroid hormone to elevate cytosolic Ca2+ ([Ca2+]i). However, other hormones increase [Ca2+]i in the absence of [Ca2+]o. These differences may arise from a diversity of signal transduction pathways acting on external and internal Ca2+ pools. However, Ca2+ influx may be necessary to expedite and maintain the rise of [Ca2+]i for a period after the initial surge. In this study, F- was used to probe the roles of intracellular Ca2+ mobilization, Ca2+ influx, and phosphoinositide (PI) hydrolysis on the surge of [Ca2+]i in rat proximal tubules. In the presence of external Ca2+; 1-20 mM F- evoked incremental rises of [Ca2+]i in tubules loaded with aequorin. Whereas 10 mM F- increased [Ca2+]i in the absence of [Ca2+]o, the time constant for the [Ca2+]i surge was increased. These findings are consistent with a role of Ca2+ influx on the effect of F- on [Ca2+]i. Indeed, 10 mM F- also enhanced the uptake of 45Ca2+, and promoted Ca2+ influx in aequorin- and fura-2-loaded, Ca(2+)-deprived tubules. In tubules, F- also activated PI hydrolysis with a time course that paralleled Ca2+ mobilization. The effect of F- on [Ca2+]i was not altered when the 39-kDa pertussis toxin substrate was inactivated with the toxin. This G protein was most likely Gi, because prostaglandin E2, an activator of Gi in tubules, dissociated the pertussis toxin-sensitive protein. The results support the notion that activation of a signal-transduction complex, the F- substrate, causes Ca2+ influx, mobilizes internal Ca2+, and activates PI hydrolysis in rat proximal tubules.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensin II receptor subtypes in renal cortex of rats and rhesus monkeys
Authors: Gibson R. E. , Thorpe H. H. , Cartwright M. E. , Frank J. D. , Schorn T. W. , Bunting P. B. , Siegl P. K.
Published: December 2017

The angiotensin II (ANG II) receptor has recently been shown to exhibit subtypes with respect to antagonist binding. Of particular interest are the potent nonpeptide antagonists, DUP 753 and PD 121981, which exhibit selectivity for the subtype 1 (AT1) and subtype 2 (AT2) receptors, respectively. We used these high-affinity antagonists in competition with 125I-[Sar1,Ile8]ANG II to determine autoradiographically the distribution of these ANG II-receptor subtypes in the renal cortex of rats and rhesus monkeys. Binding of the radioligand to receptor in sections of rat renal cortex was inhibited by DUP 753; inhibition by PD 121981 was not detected. By contrast, AT1 and AT2 receptors are present in the renal cortex of rhesus monkeys in regionally distinct structures. DUP 753 inhibited binding to the ANG II receptor in glomeruli. PD 121981 inhibited binding to arterial smooth muscle and the juxtaglomerular (JG) apparatus. The JG apparatus also exhibits radioligand binding, which is inhibited by DUP 753. The effect of DUP 753 and PD 123177 (a more water-soluble analogue of PD 121981) on changes in plasma renin activity was examined to determine if one or both of these subtypes participate in the ANG II-mediated negative feedback of control of renin release. Although DUP 753 increased plasma renin activity to the same extent as the angiotensin-converting enzyme inhibitor, enalaprilat, in rats and rhesus monkeys, the AT2 antagonists did not affect renin release in either species. Thus both subtypes of ANG II receptor are present in rhesus monkey cortex, but a function for only the AT1 subtype was demonstrated.
Stimulatory effect of calcium on metabolism and its sensitivity to pH in kidney mitochondria
Authors: Drewnowska K. , Schoolwerth A. C.
Published: December 2017

The relationship between mitochondrial matrix free Ca2+ concentration ([Ca2+]m) and pH was evaluated by incubating isolated rat kidney mitochondria with different extramitochondrial Ca2+ concentrations ([Ca2+]e) at medium pH (pHe) 7.0 and 7.4. [Ca2+]m was monitored using the fluorescent signal from mitochondria loaded with the Ca2+ indicator fura 2. The changes in [Ca2+]m were compared with alpha-ketoglutarate dehydrogenase (alpha-KGDH) flux, measured as O2 consumption (nmol.min-1.mg protein-1) from 185 microM alpha-ketoglutarate (alpha-KG). The apparent dissociation constant of the matrix fluorescent probe for Ca2+ was determined in each experiment and was 323 +/- 45 nM (n = 14). When mitochondria were exposed to [Ca2+]e below 160 nM, [Ca2+]m was greater at pHe 7.0 than at pHe 7.4. However, above 160 nM [Ca2+]e, [Ca2+]m plateaued at pHe 7.0 but rose progressively at pHe 7.4. Increasing [Ca2+]m by consecutive additions of Ca2+ to the medium had a significantly more pronounced acceleratory effect on alpha-KG oxidation at pHe 7.0 than at pHe 7.4. Kinetic analysis of alpha-KGDH revealed a 45% decrease in the Michaelis constant (Km) for alpha-KG at pHe 7.0, but the Km was unchanged at pHe 7.4 with elevation of [Ca2+]m from 32 to 751 nM. Maximal velocity (Vmax) increased significantly at both pHe values. Half-maximal alpha-KG oxidation occurred at [Ca2+]m of 76 +/- 11 nM and 105 +/- 31 nM at pHe 7.0 and 7.4, respectively. These studies demonstrate a direct, pH-sensitive correlation between [Ca2+]e and [Ca2+]m; [Ca2+]m changed over a range that may regulate alpha-KGDH flux in intact kidney mitochondria.(ABSTRACT TRUNCATED AT 250 WORDS)
Ba(2+)-sensitive K+ channels in basal membrane of confluent Madin-Darby canine kidney cells
Authors: Wang X. Y. , Harris P. J. , Kemm R. E.
Published: December 2017

A method is described for gaining access to the basolateral membranes of confluent Madin-Darby canine kidney (MDCK) cells by surgical reflection of the cell layer overlying fluid-filled domes. Single-channel recordings from cell-attached inside-out and outside-out configurations revealed two K+ channels located in the basal membranes of the highly differentiated monolayers. With 140 mmol/l KCl in pipette, the intermediate-conductance K+ channel displayed outward rectification in cell-attached configuration with channel conductances of 65 pS for outward part and 17 pS for inward part. In excised-patch recording, this channel had a conductance of 92 pS with 140 mmol/l KCl on the extracellular side of the patch and 5 mmol/l KCl on the cytosolic side. The maximum conductance obtained in symmetrical KCl (140 mmol/l) solution was 140 pS. Ba2+ (1 mmol/l) and tetraethylammonium (5 mmol/l) blocked this channel reversibly. Channel open probability (Po) was reduced from 0.41 at cytosolic pH 7.4 to 0.14 at pH 6.8 and increased to 0.64 at pH 8.0. The channel activity was significantly inhibited by elevation of intracellular Ca2+. A small-conductance K+ channel was also observed mainly in excised patches with single-channel conductance of 48 pS in symmetrical KCl solutions. However, the activity of this channel was partially obscured by the intermediate-conductance K+ channel and further analysis was not possible. A physiological role of these channels in mediating K+ recycling through the monolayer is suggested.
An NMR study of cellular phosphates and membrane transport in renal proximal tubules
Authors: Chobanian M. C. , Anderson M. E. , Brazy P. C.
Published: December 2017

Technical limitations in the measurement of cellular phosphates have hindered studies of interrelationships between cellular Pi, its transport, and its metabolism in renal proximal tubule (PT) cells. We have developed a noninvasive 31P-nuclear magnetic resonance (NMR) probe-perifusion system to measure cellular Pi and have utilized this system to investigate relationships in canine PT cells between the membrane transport and the cellular content of Pi. With 1.2 mM Pi in the extracellular medium, the cellular Pi content of PT averaged 4.94 +/- 0.55 nmol/mg protein. Inhibition of Pi uptake by removal of extracellular Pi rapidly decreased all cellular phosphate compounds to values that were between 55 and 85% of control. Partial replacement of extracellular Pi (0.4 mM) increased cellular phosphates up to 84-100% of control values. Inhibition of Na(+)-K(+)-adenosinetriphosphatase uptake by the addition of ouabain failed to change either cellular Pi or organic phosphates. Reducing the basolateral membrane potential with the addition of barium chloride increased cellular Pi content by nearly 30%. Maximal contents of cellular Pi and ATP were achieved at 0.4 mM Pi in the presence of an inwardly directed Na+ gradient and at 0.8 mM Pi in its absence. These data indicate that cellular Pi content in canine PT is regulated by Na(+)-dependent and -independent transport mechanisms and by the membrane potential across the basolateral membrane. Lastly, cellular ATP content was found to be directly proportional to the cellular Pi content over a physiological range.
Caffeine modulates Ca2+ receptor activation in isolated rat osteoclasts and induces intracellular Ca2+ release
Authors: Shankar V. S. , Pazianas M. , Huang C. L. , Simon B. , Adebanjo O. A. , Zaidi M.
Published: December 2017

A ryanodine-sensitive pathway is involved in intracellular Ca2+ release in response to activation of the osteoclast cell surface Ca2+ receptor. We now report that the ryanodine-receptor modulator, caffeine itself released intracellularly stored Ca2+ and, strongly inhibited Ca2+ release triggered in response to Ca(2+)-receptor activation by Ni2+, a surrogate cation agonist. Caffeine yielded a bell-shaped concentration-response curve (0.005-2 mM) and displayed use-dependent inactivation. Furthermore, responses to caffeine were abolished on prior application of Ni2+ (5 mM). Subthreshold (0.005 mM) caffeine concentrations abolished Ni(2+)-induced elevations in the cytosolic Ca2+ concentration ([Ca2+]). However, in a Ca(2+)-free, ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid-containing solution (extracellular [Ca2+] < 10 nM), caffeine (0.5 mM) neither elevated [Ca2+] nor inhibited the response to Ni2+. Finally, when caffeine was applied to intercept the plateau phase of the cytosolic Ca2+ signal triggered by extracellular Ca2+ elevation (10 mM), a rapid but reversible inactivation followed. These studies strongly indicate the existence of a caffeine-sensitive mechanism for the release of intracellularly stored Ca2+ in the osteoclast.
IMCD cells cultured from Dahl S rats absorb more Na+ than Dahl R rats
Authors: Husted R. F. , Takahashi T. , Stokes J. B.
Published: December 2017

Dahl salt-sensitive (S) rats develop hypertension in response to a high-salt diet, whereas Dahl salt-resistant (R) rats do not. There is good evidence that the Dahl S kidneys have diminished natriuretic capacity. We studied the rate of Na+ transport by primary cultures of the inner medullary collecting duct from these two strains to determine whether there were intrinsic differences. Monolayers obtained from prehypertensive S rats transported Na+ at twice the rate as monolayers from age-matched R rats. Mineralocorticoid and glucocorticoid hormones increased Na+ transport from both strains; the S rat monolayers always displayed higher transport rates than R rat monolayers with the same treatment. The Na+ entry pathway in both S and R rat monolayers was via an Na+ channel. The difference in Na+ transport was not explained by a difference in the metabolism of corticosterone, ATP content, citrate synthase activity, ultrastructural appearance, or rate of maturation. Monolayers from S rats tended to have higher protein and DNA content, but these differences could not account for the difference in Na+ transport. Anion secretion in response to adenosine 3',5'-cyclic monophosphate agonists was similar. These results demonstrate intrinsic differences in renal tubular cells that may play an important role in the pathogenesis of salt-sensitive hypertension.
Protein kinase C stimulates the small-conductance K+ channel in the basolateral membrane of the CCD
Authors: Lu M. , Wang W.
Published: December 2017

We have used the patch-clamp technique to study the regulation of the activity of the basolateral small-conductance K+ channel (SK) in the cortical collecting duct (CCD) of the rat kidney. Addition of 50-75 nM calphostin C, an agent which specifically inhibits protein kinase C (PKC), reduced channel activity by 90% in cell-attached patches. In contrast, addition of 1 microM phorbol 12-myristate 13-acetate, a stimulator of PKC, led to addition of “new” K+ channel currents in 9 of 20 patches in the basolateral membrane of the CCD, and the mean increase in NP0, a product of channel number (N) and open probability (Pzero), was 0.90 in these 9 patches. However, application of 1 nM exogenous PKC had no significant effect on channel activity in inside-out patches, suggesting that the PKC effect on the activity of the SK observed in cell-attached patches was not a result of a membrane-delimited action, such as a direct phosphorylation of the SK or closely associated proteins. The effect of calphostin C on the SK can be reversed by addition of either 10 microM S-nitroso-N-acetylpenicillamine, a donor of nitric oxide, or 100 microM 8-bromoguanosine 3',5'-cyclic monophosphate. In addition, the inhibitory effect of calphostin C on the SK was completely abolished by pretreatment of the cells with 1 microM okadaic acid, an inhibitor of protein phosphatase. However, 100 microM N omega-nitro-L-arginine methyl ester, an agent that inhibits nitric oxide synthases (NOS), blocked the SK in cell-attached patches in the presence of okadaic acid, suggesting that the effect of okadaic acid on calphostin C-induced inhibition of the SK was a step before formation of nitric oxide. We conclude that PKC is involved in the stimulation of the SK and that the effect of PKC on the SK may be mediated by regulation of NOS activity in the CCD of the rat kidney.
Functional differences between rabbit and human Na(+)-dicarboxylate cotransporters, NaDC-1 and hNaDC-1
Authors: Pajor A. M. , Sun N.
Published: December 2017

The rabbit and human Na(+)-dicarboxylate cotransporters, NaDC-1 and hNaDC-1, were expressed in Xenopus oocytes, and the transport of succinate, citrate, and glutarate was compared. Both transporters had similar affinities for succinate and glutarate, with Michaelis-Menten constant (K(m)) values of approximately 0.5- 0.8 mM (succinate) and 6-7 mM (glutarate), verifying that they are low-affinity sodium-dependent dicarboxylate transporters. The two transporters differed in their handling of citrate. At pH 7.5, the K(m) value for citrate was 0.9 mM in the rabbit NaDC-1 and 7 mM in the human hNaDC-1. However, the human transporter was more sensitive to pH than the rabbit. At pH 5.5, the K(m) value for citrate decreased to 1.2 mM in hNaDC-1 and decreased to 0.3 mM in the rabbit transporter. Both transporters had Hill coefficients between 1.6 and 2.1, suggesting that multiple sodium ions are coupled to the transport of divalent anions. However, the human transporter, hNaDC-1, had a lower apparent affinity for sodium (KNa, 78 mM) than the rabbit transporter (KNa, 41 mM). In addition, the human hNaDC-1 was relatively insensitive to inhibition by lithium, furosemide, and flufenamate compared with the rabbit NaDC-1. The differences between the human and rabbit transporters may account for observed differences in renal handling of citrate between species.
Relationships between fast vital capacity and various timed expiratory capacities
Authors: Miller William F. , Johnson Robert L. , Wu Nancy
Published: December 2017

Fast vital capacity, 0.5-second, 0.75-second and 1.0-second timed expiratory capacities were measured with a Gaensler-Collins timed vitalometer in 153 healthy subjects, including equal numbers of males and females ranging in age from 20 through 60 years. The timed expiratory capacities (TEC) were found to constitute a fairly constant proportion of the vital capacity (VC) and the linear relationship of the TEC to the VC establishes the validity of using the ratio TEC/VC as a means of expressing this function for purposes of comparative analyses of function. The mean 0.5-second EC ratio was found to be 67.8%, the 0.75-second EC 77.3%, and the 1.0-second EC 83.9% with no variation between sexes and no significant age regression in the 0.5-second EC ratio. Values obtained by this method were comparable to those obtained by pneumotachographic and special spirometric techniques (Bernstein). Formulas for predicting the expected fast vital capacity for both males and females, using height and age as parameters, were calculated from these data to provide more accurate prediction of the VC in both sexes when the VC is measured by this commonly used method. A convenient nomogram was constructed for this purpose.

Submitted on June 17, 1958
Solubility of ammonia in human plasma
Authors: Jacquez John A. , Poppell J. William , Jeltsch Rudolph
Published: December 2017

The solubility of ammonia in pooled human plasma was measured by a constant flow equilibration method. The solubility coefficient in liter NH3 (STPD) per liter plasma at 1 mm Hg partial pressure of ammonia was found to be 1.07, .91, .83 and .79 at 32, 37, 40.5 and 41.5℃, respectively.

Submitted on September 18, 1958
A method for dealing with data concerning uneven ventilation of the lung and its effects on blood gas transfer
Authors: Briscoe William A.
Published: December 2017

This is a consideration of the relationships between the uneven ventilation of the lung and the arterial oxygen saturation and CO2 tension. In the simplest case, the lung is considered to contain only two differently ventilated and perfused components. Graphic methods are developed for dealing with situations of this type and illustrated by application to the data obtained in a normal subject. Some of the methods outlined here can be applied in situations where the lung is composed of three or more differently ventilated and perfused components. In the normal subject considered here, the uneven ventilation of the lung is compatible with A-a gradients of 6 and 0.8 mm for O2 and CO2, respectively.

Submitted on October 3, 1958
Relative volume changes between lobes of the lung
Authors: Koler John J. , Young A. C. , Martin C. J.
Published: December 2017

Lobarspirometry was used to measure the relative volume changes between pulmonary lobes in normal human subjects. The flow resistive properties of the system were obviated by having the subject interrupt flow throughout the vital capacity range. The plot of relative volume changes of the upper and the lower lobe during inspiration was curvilinear in all subjects. Expiration had a less consistent pattern, but most often the upper lobe, rather than the lower lobe, contributed more to late expiration. The plot of volume differences between lungs did not reveal a consistent relationship. However, in contrast to the plot of the lobes, the plot of the lung volumes was often linear. The breath-holding points frequently showed a ‘creep’ phenomenon where the volume changes between lobes were opposite in direction or where the volume in one lobe remained constant, while that in the other was increasing or decreasing. Changes in body position did not affect these curves. The occurrence of unequal volume changes must mean that the mechanical properties of the units differ or that they are exposed to different stresses.

Submitted on August 19, 1958
Relationship between pain and tissue damage due to thermal radiation
Authors: Stoll Alice M. , Greene Leon C.
Published: December 2017

Sites on the volar surfaces of the forearms of human subjects were blackened with India ink and exposed to thermal irradiances of from 50 to 400 mcal/cm2 sec. The exposure time and skin temperature at which threshold pain occurred, and which produced minimal blistering within 24 hours, were noted. The thermal inertia (k⍴c) of the skin was shown to vary directly with the level of irradiance. The receptors effective in mediating the pain sensation were calculated to be at a depth of approximately 200 μ and to have a threshold of approximately 43.2℃. Tissue damage rates with respect to temperature were derived empirically so that damage integrated over the time for which skin temperature was elevated over the pain threshold was equated to unity. The substitution of the ratio of these rates with respect to temperature for the stimulus ratio, in the prediction of the observed discriminable steps in pain sensation intensity, yielded faithful reproduction of the just noticeable differences observed for pain through the range of this sensation.

Submitted on September 17, 1958
Pulmonary function in the normal male
Authors: Holmes Edward L.
Published: December 2017

Selected pulmonary function tests, total vital capacity (TVC), 1.0 second expiratory capacity (EC) and total expiratory time were determined in 130 healthy males age 20–25 years. The mean TVC as measured in the sitting position was 5.09 l. ± S.E. 0.05. The mean value was significantly higher than predicted, using the formula of West. TVC increased with increasing body surface and height. Especially good correlation was seen between TVC and essential body mass (EBM) where an essentially linear relationship was obtained. Data from this study on a narrow age group indicates that the normal may deviate from the mean by as much as 20%. The mean 1.0 second EC was 90.8% ± S.E. 0.44 of the TVC. This was somewhat higher than has been reported. The total expiratory time was 1.63 seconds ± S.E. 0.03. There was no correlation of total expiratory time with any body measurement.

Submitted on October 27, 1958
Pulmonary blood volume determined by a radioactive tracer technique
Authors: Weissler Arnold M. , McCraw Burley H. , Warren James V.
Published: December 2017

A semiquantitative technique for assaying shifts in intrapulmonary blood volume is described. The method consists of the external monitoring of radioactivity over the anterior thorax after the intravenous administration of radioactive iodinated albumin utilizing a sensitive scintillation counter with a focusing collimator attachment. While this method does not yield the quantitative data of the indicator dilution and body plethysmographic techniques, it offers the advantage of confining observations to the intrapulmonary rather than the intrathoracic blood volume. Employing this technique, the effects of the upright posture, peripheral venous pooling and the Valsalva maneuver have been studied. A fall in estimated pulmonary blood volume was noted with each procedure, averaging 28%, 9% and 11%, respectively, below control levels.

Submitted on January 16, 1959
Discrepancy between body and venous hematocrits. Dilution curves of simultaneously administered I131-HSA and Cr51-labeled erythrocytes in man
Authors: Tuckman John , Finnerty Frank A. , Buchholz Joachim H.
Published: December 2017

The difference between direct and indirect plasma volumes was studied in man by the analysis of detailed dilution curves following simultaneous administration of I131-HSA and Cr51-RBC-labeled erythrocytes. These results showed: 1) the discrepancy between the apparent direct (I131-HSA) and indirect (Cr51-RBC) plasma volumes became evident with the first appearance of recirculation. 2) The apparent ratio of body to anticubital vein hematocrits remained approximately the same during the remainder of the 2-hour procedure. Two hypotheses were considered as possible explanations for the rapid appearance of the greater direct plasma volume: a) a rapidly equilibrating extravascular space entirely permeable to plasma protein but not to red blood cells and b) intravascular areas of low hematocrits. The latter hypothesis was considered the more probable.

Submitted on November 5, 1958
Counterrolling of the eyes and its dependence on the magnitude of gravitational or inertial force acting laterally on the body
Authors: Woellner Richard C. , Graybiel Ashton
Published: December 2017

Counterrolling of the eyes was measured in five healthy persons when inclined on a tilt-chair and when exposed to a change in direction of force on a human centrifuge. For equivalent changes in direction of force incident to the subject, the magnitude of the force was greater on the centrifuge. When the amount of roll was plotted as a function of the incident angle of force, divergent curves were obtained for tilt-chair and centrifuge data. When the amount of roll was plotted as a function of magnitude of laterally-acting force as the independent variable, a single curve resulted indicating a straight line relation within the range of 1 g. These findings not only constitute definitive proof that the counterrolling reflex can be released by gravitational (and inertial) force but also are consistent with the current theory of the functioning of the otolith organs.

Submitted on January 20, 1959
Aortic blood flow in dogs during treadmill exercise
Authors: Franklin Dean L. , Ellis Richard M. , Rushmer R. F.
Published: December 2017

Instantaneous blood flow through the thoracic aorta was monitored continuously during spontaneous activity in intact dogs by means of a new, pulsed, ultrasonic flowmeter. Integrated flow per stroke, accumulated flow per unit time and heart rate were simultaneously derived by means of electronic computers. During treadmill exercise at 3 mph on a 5% grade, the heart rate increased by two- or threefold, but the aortic flow per stroke was only slightly increased. This observation was confirmed by direct measurements, of left ventricular diameter. An increase in stroke volume is not an essential feature of the cardiac response to exercise in these experiments.

Submitted on December 15, 1958
Maximum oxygen intake and maximum heart rate during strenuous work
Authors: Wyndham C. H. , Strydom N. B. , Maritz J. S. , Morrison J. F. , Peter J. , Potgieter Z. U.
Published: December 2017

At least five separate determinations were made of oxygen intake and heart rates at various levels of work on a bicycle ergometer, up to and above the maximum level of O2 intake of four highly trained men. From these measurements it has been possible to fit appropriate curves to the experimental data and test for their goodness of fit. At low rates of work a straight line fits both O2 intake and heart rate plots against work rate, but at high work rates the curves tend toward an asymptote. The O2 intake curve reaches its asymptote more slowly than does the heart rate; hence, if heart rate is plotted against O2 intake and a straight line fitted and extrapolated to the maximum value of heart rate, the O2 intake at this value is an underestimate of the actual measured maximum O2 intake. Because of the characteristic slope of the best-fit curve of oxygen intake against work rate, the criteria proposed by some earlier investigators for the level of O2 intake at which the maximum is unequivocally attained, is open to criticism. An alternative is proposed. The maximum levels of O2 intake and maximum heart rate of trained men studied over 4 months is remarkably constant, having average coefficients of variation of 4.3% and 3.5%, respectively.

Submitted on December 2, 1958
Biologic assay of a thrombosis-inducing activity in human serum
Authors: Wessler Stanford , Reimer Stanley M. , Sheps Mindel C.
Published: December 2017

The systemic infusion of thrombin-free human serum induces massive thrombosis in rabbit vein segments containing stagnant blood far removed from the site of infusion. In contrast, carefully collected human plasma is inert in this system. The data indicate that this phenomenon of in vivo thrombosis is quantitatively related to the amount of serum infused and forms the basis for a bioassay of the thrombosis-inducing activity. This bioassay, in providing a technique for detecting and quantitating the thrombosis-inducing activity of normal human serum, may facilitate separation of this activity from other recognized coagulation factors and serve as a guide to its ultimate isolation, purification and characterization.

Note:

(With the Technical Assistance of Marjorie Nickles, Mary-Lou Bloede, Bela J. Szalai and Rita J. Nickerson)

Submitted on June 18, 1959
Mathematical analysis of the time course of alveolar CO2
Authors: Yamamoto William S.
Published: December 2017

Continuous respiratory CO2 gas exchange is simulated theoretically by means of a suitably constructed dilution equation of the form (See PDF) where C is instantaneous concentration, Q quantity flow, and V volume flow. When such an equation is constrained in its numerical solutions to yield inflow-outflow equality for CO2 in the steady state, solutions for CO2 as a time series are found to differ according to whether the site of entry of CO2 is entirely by venous blood or is also by inspired CO2. In the case of entry via the venous blood, increasing CO2 is eliminated while keeping mean CO2 constant with increasing fluctuations about this mean. In the case of entry via the lung, increasing CO2 is eliminated by raising the mean and at the same time oscillations diminish.

Submitted on August 13, 1959
Regulation of human plasma fluoride concentration
Authors: Singer Leon , Armstrong W. D.
Published: December 2017

There is a constancy of plasma fluoride content of individuals who use communal water within the range 0.15– 2.5 ppm fluoride. With an intake of 5.4 ppm of fluoride in the communal water there is a slight but significant elevation of the plasma concentration. There is no evidence of a marked or prolonged rise of plasma fluoride content following the ingestion of 1.0 mg fluoride or of a diurnal variation of plasma fluoride content. The mean plasma fluoride concentration of hospitalized patients is not different from that of normal people. The factors relating skeletal fluoride content to small and short-term rises of plasma fluoride concentration are discussed.

Submitted on November 19, 1959
Augmentor action of the sympathetic cardiac nerves in man
Authors: Randall Walter C. , McNally Howard
Published: December 2017

During surgical procedures involving the upper thoracic sympathetic trunk in man, systolic and diastolic pressures were recorded during electrical stimulation. Significant and frequently profound elevation in systolic pressure, with little change in diastolic pressure, resulted in a marked increase in pulse pressure which has been designated as an augmentor response. Cardiac acceleration was an accompanying but less impressive response. The upper four or five thoracic segments mediate both the chronotropic and the inotropic action of the sympathetics but the T1 to T3 levels are the most significant. Corollary observations in animal experiments indicate the response is related to increased force of myocardial contraction with consequent increased systolic ejection.

Submitted on February 1, 1960
Heat production from shivering
Authors: Iampietro P. F. , Vaughan J. A. , Goldman R. F. , Kreider M. B. , Masucci F. , Bass David E.
Published: December 2017

Healthy young men were exposed, nearly nude, for 2 hours or less to various environmental conditions (dry-bulb temperature, 90°–20°F; windspeed, μ1, 5, 10 mph). Oxygen consumption was recorded at intervals during exposure. The results show that even under conditions where no visible shivering was observed, there was an increase in heat production. Exposure to very low temperatures (20°F) with low winds did not evoke the largest increases in heat production. The greatest mean heat production (370 Cal/hr.) was associated with the highest windspeed (10 mph), and this value approached the maximum heat production which can be attained by shivering (mean value about 425 Cal/hr.). Thus, increasing the windspeed had a relatively greater impact on heat production than decreasing the dry-bulb temperature. The relationships between heat production and windspeed and heat production and dry-bulb temperature were nonlinear.

Submitted on February 8, 1960
Estimation of body surface area of extremely obese human subjects
Authors: Tucker Garrett R. , Alexander James K.
Published: December 2017

The body surface areas of one normal and four extremely obese human subjects have been estimated by three methods: a) direct measurement by a method similar to that which Du Bois described; b) calculation from the Du Bois height-weight formula; and c) calculation from the Du Bois linear formula. The values for the total body surface area of the obese subjects calculated from the height-weight formula varied up to 11% below those that were directly measured. The values for the total body surface area obtained with the linear formula ranged between 13% and 20% above the direct measurements, this being almost entirely due to discrepancies in the trunk and in the thigh estimations. It has been concluded that estimation of the body surface area oxf extremely obese subjects by the Du Bois height-weight formula is satisfactory when considered in relation to the accuracy of the physiologic measurements with which it is generally used. Because of the unusual body form the Du Bois linear formula has been found unsatisfactory for this group.

Submitted on March 1, 1960
Physiological comparison of three types of ergometry
Authors: Bobbert A. C.
Published: December 2017

A physiological comparison of cycling, cranking and walking has been made, using in all experiments the same subjects and methods. In cycling and cranking energy expenditure increases with work load in a rectilinear way, the energy expenditures being always higher in cranking. In treadmill walking energy expenditure per kilogram of body weight rises curvilinearly both with increasing speed and grade. In cycling, cranking and walking there are nearly the same relations between heart rate and metabolism. Ventilation in cranking always exceeds that in walking and cycling at the same level of oxygen consumption. The curve of ventilation versus oxygen consumption shows a steeper rise in cranking. In level and grade walking ventilation increases curvilinearly with oxygen consumption.

Submitted on September 17, 1959
Ventilation and circulation after fluid aspiration
Authors: Halmagyi Denis F. J. , Colebatch H. J. H.
Published: December 2017

Ventilated volumes, arterial oxygen content and carbon dioxide tension, cardiac output, ‘effective’ pulmonary capillary flow, systemic arterial, pulmonary arterial and pulmonary arterial wedge pressures were determined before and after the intratracheal administration of 1–3 ml/kg body weight of fresh and sea water in 23 intact and 14 vagotomized sheep in light thiopentone anesthesia. Five untreated animals served as controls. A precipitous fall and a prolonged depression of arterial oxygen saturation was observed, largely independent of the amount of fluid inhaled. Hypoxemia was due to a gross increase in venous admixture resulting from the perfusion of large unventilated portions of the lungs. Fluid aspiration was also followed by a significant degree of pulmonary hypertension caused by arteriolar constriction in the lungs. Pulmonary hypertension was found to be unrelated to hypoxia.

Submitted on October 15, 1959
Some effects of breathing oxygen before and after exercise
Authors: Elbel Edwin R. , Ormond Donald , Close Donald
Published: December 2017

Athletes in better than average physical condition breathed 100% O2 during 6 minutes of rest, air during 5 minutes of treadmill running at 8 m.p.h. and O2 during 19 minutes of recovery. The results were compared with a control procedure in which the same subjects breathed air throughout. It was found that the experimental procedure: a) did not significantly facilitate recovery as based upon payment of O2 debt, measured by a closed-circuit spirometric method; b) depressed the pulse rate during the first 2 minutes of exercise and during the recovery period; c) caused the respiratory rate to increase at rest, to decrease during the initial part of the recovery period, and to increase during the latter part of the recovery period; d) increased the percentage of O2 saturation of blood hemoglobin, as measured by an ear oximeter, during rest and recovery. Lower oximeter readings were found during the latter part of the exercise period.

Submitted on July 26, 1960
Anatomic distribution of induced changes in blood volume, evaluated by regional weighing
Authors: Fell Colin , Rushmer Robert F.
Published: December 2017

Anesthetized cats were supported on electronic scales placed under the head, thorax, abdomen and hindquarters, and the changes in the weights supported by these scales were recorded while blood was withdrawn and while blood and saline were infused. The recorded changes in weight indicated that the abdomen and the thorax both contributed significantly to the volume of withdrawn blood and that infused fluids were taken up by both regions. The blood volume of neither region was conserved at the expense of the other. The average weight change of the hindquarters was 5–10% of the over-all response, but in many cases the weight of the hindquarters was stable during an experiment. The average error in measurement of changes in total body weight was 6%. Interactions between the scales were evaluated by injecting mercury into pouches placed at specific anatomic locations. Interactions did occur, but were not so great as to invalidate the method.

Submitted on September 16, 1960