Increased renal vascular reactivity to ANG II after unilateral nephrectomy in the rat involves 20-HETE.

This study examined the role of intrarenal ANG II in the renal vascular reactivity changes occurring in the remaining kidney undergoing adaptation following contralateral nephrectomy. Renal blood flow responses to intrarenal injections of ANG II (0.25 to 5 ng) were measured in anesthetized euvolemic male Wistar rats 1, 4, 12, and 24 wk after uninephrectomy (UNX) or sham procedure (SHAM). At week 4, renal vasoconstriction induced by 2 ng ANG II was greater in UNX (69 +/- 5%) than in SHAM rats (50 +/- 3%; P < 0.01). This response was inhibited, by 50 and 66%, and by 20 and 25%, in SHAM and UNX rats, after combined injections of ANG II and losartan, or PD-123319 (P < 0.05), respectively. Characteristics of ANG II receptor binding in isolated preglomerular resistance vessels were similar in the two groups. After prostanoid inhibition with indomethacin, renal vasoconstriction was enhanced by 42 +/- 8% (P < 0.05), only in SHAM rats, whereas after 20-HETE inhibition with HET0016, it was reduced by 53 +/- 16% (P < 0.05), only in UNX rats. These differences vanished after concomitant prostanoid and 20-HETE inhibition in the two groups. After UNX, renal cortical protein expression of cytochrome P-450 2c23 isoform (CYP2c23) and cyclooxygenase-1 (COX-1) was unaltered, but it was decreased for CYP4a and increased for COX-2. In conclusion, renal vascular reactivity to ANG II was significantly increased in the postuninephrectomy adapted kidney, independently of protein expression, but presumably involving interactions between 20-HETE and COX in the renal microvasculature and changes in the paracrine activity of ANG II and 20-HETE.

Changes in renal haemodynamics induced by indomethacin in the rat involve cytochrome P450 arachidonic acid-dependent epoxygenases.

A significant renal vasodilation was observed previously after an acute cyclo-oxygenase (COX) inhibition induced with indomethacin. Because this effect could be due to COX-dependent intrarenal metabolization of arachidonic acid through cytochrome P450 (CYP450) pathways, the aim of the present study was to investigate, in vivo, possible interactions between COX and CYP450 mono-oxygenases. Mean arterial pressure (MAP) and renal blood flow (RBF), using an electromagnetic flow transducer for RBF evaluation, were measured continuously in 71 anaesthetized euvolaemic rats. Appropriate solvents (vehicle), 3 mg/kg indomethacin, 17-octadecynoic acid (17-ODYA; 2 mmol/L), either miconazole (MI; 1.5 mmol/L) or N-methylsulphonyl-6-(2-propargyloxyphenyl)hexanamide (MS-PPOH; 5 mg/kg) and N'-hydroxyphenylformamidine (HET0016; 5 or 10 mg/kg) were administered to inhibit either COX, CYP450 mono-oxygenases, epoxygenases or hydroxylase, respectively. The CYP450 and COX inhibitors were also combined as follows: 17-ODYA/indomethacin, MI (or MS-PPOH)/indomethacin, HET0016/indomethacin and indomethacin/HET0016. Mean arterial pressure and RBF were not modified by vehicle, 17-ODYA or MI (or MS-PPOH). However, MAP decreased slightly (P < 0.05; paired t-test, 5 d.f.) and RBF increased transiently (P < 0.05; anova, 5 d.f.) after HET0016. In contrast, MAP decreased by 10 mmHg (P < 0.05) and RBF increased by 10% (P < 0.05) after indomethacin. This enhancement was prevented by 17-ODYA or MI (or MS-PPOH), but not by HET0016. Moreover, RBF increased step-wise to 21% in the indomethacin/HET0016 experiment (P < 0.05). Consequently, changes from baseline in renal vascular resistance differed among treatments, averaging -2 +/- 3 (vehicle), -13 +/- 3 (indomethacin; P < 0.05 vs vehicle), -4 +/- 3 (17-ODYA/indomethacin), -3 +/- 4 (MI or MS-PPOH/indomethacin), -15 +/- 3 (HET0016/indomethacin; P < 0.05) and -22 +/- 4% (indomethacin/HET0016; P < 0.05). In conclusion, these results demonstrate that the renal vasodilation induced by indomethacin can be prevented by prior inhibition of CYP450 mono-oxygenases and further suggest that the CYP450 epoxygenases pathway may prevail.

Endothelin resets renal blood flow autoregulatory efficiency during acute blockade of NO in the rat.

Renal blood flow (RBF) autoregulatory efficiency may be enhanced during NO inhibition in the rat, as recently reported. Under these conditions, endothelin (ET) synthesis and release may be increased. Our purpose was therefore to determine the role of ET in RBF autoregulatory changes induced by NO inhibition. To address this point, ET(A/B) receptors were blocked in anesthetized rats with bosentan, or selectively with BQ-610 or BQ-788. NO synthesis was inhibited with N(G)-nitro-L-arginine methyl ester (L-NAME). Mean arterial pressure (MAP) was decreased after bosentan (-10 mmHg; P < 0.01) or increased after L-NAME (25 mmHg; P < 0.001). RBF measured with an electromagnetic flow probe was reduced by L-NAME (-50%) and by BQ-788 (-24%). The pressure limits of the autoregulatory plateau (P(A) approximately 100 mmHg) and of no RBF autoregulation (P(o) approximately 80 mmHg) were significantly lowered by 15 mmHg after L-NAME but were unchanged after bosentan, BQ-610, or BQ-788. During NO inhibition, autoregulatory resetting was completely hindered by bosentan (P(A) approximately 100 mmHg) and by ET(B) receptor blockade with BQ-788 (P(A) approximately 106 mmHg), but not by ET(A) receptor blockade with BQ-610 (P(A) approximately 85 mmHg). These results suggest that the involvement of ET in the RBF autoregulatory resetting occurs during NO inhibition, possibly by preferential activation of the ET(B) receptor. However, the relative contribution of ET receptor subtypes remains to be further specified.

Effects of Ca(2+) channel activity on renal hemodynamics during acute attenuation of NO synthesis in the rat.

In cultured vascular muscle cells, nitric oxide (NO) has been shown to inhibit voltage-dependent Ca(2+) channels, which are involved in renal blood flow (RBF) autoregulation. Therefore, our purpose was to specify in vivo the effects of this interaction on RBF autoregulation. To do so, hemodynamics were investigated in anesthetized rats during Ca(2+) channel blockade before or after acute NO synthesis inhibition. Rats were treated intravenously with vehicle (n = 10), 0.3 mg/kg body wt N(G)-nitro-L-arginine-methyl ester (L-NAME; n = 7), 4.5 microg. kg body wt(-1). min(-1) nifedipine (n = 8) alone, or with nifedipine infused before (n = 8), after (n = 8), or coadministered with L-NAME (n = 10). Baseline renal vascular resistance (RVR) averaged 14.0 +/- 1.2 resistance units and did not change after vehicle. RVR increased or decreased significantly by 27 and 29% after L-NAME or nifedipine, respectively. Nifedipine reversed, but did not prevent, RVR increase after or coadministered with L-NAME. RBF autoregulation was maintained after L-NAME, but the autoregulatory pressure limit (P(A)) was significantly lowered by 15 mmHg. Nifedipine pretreatment or coadministration with L-NAME limited P(A) resetting or suppressed autoregulation at higher doses. Results were similar with verapamil. Intrarenal blockade of Ca(2+)-activated K(+) channels also prevented autoregulatory resetting by L-NAME (n = 8). These findings suggest NO inhibits voltage-dependent Ca(2+) channels and thereby modulates RBF autoregulatory efficiency.

[Paracrine kidney activity and homeostasis: the emergence of nitric oxide. A conceptual perspective]. / Activité paracrine du rein et homéostasie: l'émergence du NO. Une perspective conceptuelle.

In nephrology, intensive research has focused in recent years on the interplay between NO produced by the different isoforms of NO synthase (NOS) and complex renal functions. In this regard, the juxtaglomerular apparatus is of particular interest. First, it is the main site for control of renal blood flow by autoregulation and of glomerular filtration rate by tubuloglomerular feedback, as well as of renin secretion. Second, two constitutive NOS, nNOS and eNOS, are expressed, respectively, in the macula densa cells and in the endothelium of the afferent and efferent arteriole. It was thus not unexpected that NO could interact with the physiological variables. Indeed, NO attenuates rapidly the autoregulatory efficacy of renal blood flow as well as the sensitivity of the tubuloglomerular feedback by inhibiting Ca++ influx mainly in the afferent arteriole. On the other hand, renin secretion may be stimulated as well as inhibited by NO. These opposing effects, although as yet unexplained, could be related to the source of NO. If so, the hypothetical dual effect of NO could be secondary to a difference in modulation of each NOS isoform by their specific stimuli and results in secretion or not of renin. This hypothesis seems to be applicable to changes in extracellular volume.

Measurement of changes in glomerular filtration rate induced by atrial natriuretic peptide in the rat kidney.

This study was undertaken to improve the measurement of glomerular filtration rate (GFR) during the acute diuretic phase induced by atrial natriuretic peptide (ANP), which may indeed alter the renal clearance of inulin (GFRCL) due to dead space error. A technique to measure GFR without urine collections was therefore developed in anaesthetized rats prepared as for micropuncture. To do so, arterial blood was periodically collected and renal venous blood was withdrawn simultaneously from a catheter inserted into the left suprarenal vein to determine the renal extraction coefficient of inulin (CEIN). In addition, renal blood flow (RBF) was continuously measured with an electromagnetic flow transducer fitted around the left renal artery to estimate renal plasma flow (RPF). GFR (GFRCE) was then calculated as the product of RPF and CEIN. To study the effects of ANP on GFR, rats were injected i.v. with 10 microliters of saline without (n = 6; vehicle) or with 1 microgram ANP (n = 6; ANP) and GFRCE and GFRCL were compared before and after each treatment. They did not differ significantly during baseline measurements in each experimental group and were not modified after vehicle. Similarly, RBF remained constant. In contrast, RBF and GFRCE increased rapidly and simultaneously 90 s after ANP, from 9.07 +/- 0.25 to 10.07 +/- 0.35 (12%) and from 1.209 +/- 0.188 to 1.715 +/- 0.190 ml min-1 (42%), respectively (P < 0.05). GFRCL increased to an even greater extent (88%). Moreover, the peak enhancement of GFRCL was delayed and occurred 180 s after ANP. The renal clearance of inulin was thus unduly elevated due to sudden changes in the dead space induced by the diuretic effect of ANP. In conclusion, determination of glomerular filtration rate by the method of renal extraction of inulin provided more reliable results than those achieved using the classical method of renal clearance of inulin. Moreover, it was sufficiently sensitive to detect small and transient changes in GFR induced by the injection of 1 microgram ANP.

Amplification by atrial natriuretic peptide of the haemodynamic and renal responses to an acute volumic stress in the rat.

1. The purpose of the present study was to test the effects of synthetic atrial natriuretic peptide (ANP) on renal haemodynamics and excretory capacities of salt and water in the rat during an 'acute volumic stress', which was induced by brisk disturbances of the circulatory volume. 2. To this end, 29 anaesthetized male Wistar rats were rapidly injected with 1 mL of 0.85% NaCl, repeated twice at 60 s intervals. The injectates contained no ANP (n = 5) or 1 x 0.25 (n = 6), 3 x 0.25 (n = 6), 1 x 2.5 (n = 6) or 3 x 2.5 micrograms (n = 6) ANP, added to the first injectate only (1 x) or to each injectate (3 x). Renal blood flow (RBF) was continuously measured with an electromagnetic flow transducer. 3. Renal blood flow increased transiently (approximately 30 s) by approximately 13% (P < 0.05) during each injection of saline without ANP. Addition of 0.25 or 2.5 micrograms ANP to the first injectate enhanced RBF by 21 and 35%, respectively (both P < 0.05), but did not modify the time sequence. Furthermore, addition of 0.25 microgram ANP to the second and third injectate produced an almost similar change in RBF at the end of each injection (delta RBF = 20 and 17%, respectively). In contrast, the addition of 2.5 micrograms ANP to the second and third injectate did not produce the same changes in RBF observed at the end of the first injection. The amplitude of the change in RBF was then similar to the increase in RBF induced by 1 mL saline without ANP. Mean arterial pressure (MAP) did not change significantly during repeated injections of saline alone or with addition of 0.25 microgram ANP to the first injectate. However, MAP decreased significantly (by 5, 9 and 9 mmHg) after the injection of 3 x 0.25, 1 x 2.5 or 3 x 2.5 micrograms ANP, respectively. 4. Sodium excretion was rapidly increased from 2.600 +/- 0.654 to 9.330 +/- 1.322 mumol/min after injection of 3 x 1 mL of 0.85% NaCl (P < 0.05). Thereafter, sodium excretion remained enhanced throughout the experiment, so that 70% of the sodium load injected was recovered at the end of the experiment. Atrial natriuretic peptide added to the injectates further elevated the maximal responses in diuresis and natriuresis induced by saline injections without ANP (P < 0.001). A maximal effect was observed after the addition of 2.5 micrograms ANP to the first saline solution. When the amount of sodium excreted was calculated by integrating the areas under the curve of the natriuretic responses, a relationship was established as a function of the amount of ANP added to the saline solutions. It was characterized by a threshold in the presence of 2.5 micrograms ANP added to the first injectate when the integration period was limited to 4 min 30 s and 14 min 30 s after starting the first injection of the varying test solutions. When the integration period was extended until the end of the experiment (2 h), the amount of sodium excreted in each group was further enhanced, especially after injection of 3 x 1 mL of 0.85% NaCl without ANP or with 1 x 0.25 and 3 x 0.25 microgram ANP. Differences in sodium excretion between groups were attenuated (P < 0.054, ANOVA). 5. In conclusion, our results demonstrate differential effects of synthetic ANP on renal vascular reactivity and excretory capacity. These effects were superimposed on changes induced by acute volumic stress. In particular, effects of saline injections on renal vascular compliance were amplified in the presence of ANP added in varying amounts to the injectates. This amplification was limited to 2.5 micrograms ANP.

Differential effects of sulindac on renal hemodynamics and function in the rat.

Renal hemodynamics were studied using an electromagnetic perivascular flow sensor in anesthetized rats injected i.v. with vehicle, 5 or 10 mg/kg body weight (b.w.) sulindac. No hemodynamic changes occurred with vehicle (n = 6), but mean arterial pressure was significantly decreased (by 15 mmHg) with sulindac (n = 12). In the 5 mg/kg b.w. sulindac group (n = 7), renal blood flow progressively and significantly increased from 7.88 +/- 0.36 to 8.98 +/- 0.58 ml/min, except during concomitant intrarenal infusion of 3 mg/kg b.w. per h proadifen (n = 7). The pressure limits for efficient and no renal blood flow autoregulation remained unchanged (approx. 100 and 80 mmHg, respectively). In the 10 mg/kg b.w. sulindac group (n = 5), renal blood flow did not change but autoregulatory pressure limits were lowered by 10 mmHg 2 h after treatment (P < 0.025). Also, Na+ retention was marked. Prostanoid excretion in urine was significantly reduced with either dose but basal plasma renin activity was not (about 8 ng/ml per h; n = 15). When plasma renin activity was enhanced after a reduction in renal perfusion pressure (n = 21), it was decreased from 11.5 +/- 1.2 to 7.4 +/- 0.2 ng/ml per h only by 10 mg/kg b.w. sulindac (P < 0.05; n = 6). In conclusion, differential effects of sulindac on renal hemodynamics, Na+ excretion and plasma renin activity were demonstrated. Renal hemodynamic changes could be related in part to the cytochrome P-450 arachidonic acid pathway.

Dose-response analysis of acute hypotensive and renal effects of atrial natriuretic peptide in the rat.

Acute treatments with synthetic atrial natriuretic peptides induce hypotension, in which several mechanisms, including renal effects, are involved. The implication of the renal vasculature and the excretory capacities in the hypotensive action of atrial natriuretic peptides are not ascertained as yet. To address this issue, the rapid time sequence of the acute effects of atrial natriuretic peptides upon renal blood flow, mean arterial pressure, heart rate, and salt and water excretion, as well as a dose-response analysis, were investigated in 38 anesthetized euvolemic rats. Doses varying from 0.25 to 2.50 micrograms of atrial natriuretic peptide were injected i.v. in 30 sec. Each dose induced a brisk and transient increase in renal blood flow, which was maximal (13%) above 1 microgram of atrial natriuretic peptide. A small reduction in mean arterial pressure, timely related to renal vasodilation, occurred at first. It was followed by a second reduction in mean arterial pressure, which was concomitant to the maximal increases in diuresis and natriuresis. It persisted over a longer period of time. The maximal hypotensive effect (-15 mmHg) was observed above 1.5 micrograms of atrial natriuretic peptide. All effects were dose-dependent. There were no changes in heart rate. In conclusion, atrial natriuretic peptides transiently induced dose-dependent increases in renal blood flow and salt and water excretion, while the mean arterial pressure decreased stepwisely. The biphasic hypotensive effect was time-related to the renal vasodilator and diuretic effects, respectively.

Renal hemodynamics and blood flow autoregulation during acute cyclooxygenase inhibition in male rats.

After the acute inhibition of prostanoid synthesis, adjustments of renal hemodynamics may not be characterized immediately. Therefore, time-related effects of indomethacin on hemodynamics and renal blood flow (RBF) autoregulation were studied in anesthetized euvolemic male rats injected intravenously with vehicle, indomethacin (3, 4, or 5 mg/kg body wt), or meclofenamate (4 or 5 mg/kg body wt). Hemodynamics and RBF autoregulation were not influenced by vehicle injection, nor by time (n = 6). In contrast, mean arterial pressure (MAP) decreased significantly from 117 +/- 4 to 103 +/- 3 mmHg, and RBF progressively and significantly increased from 8.00 +/- 0.34 to 9.17 +/- 0.50 ml/min in the 3 mg/kg body wt indomethacin group (n = 8). Treatment with the higher doses of indomethacin (n = 9) or meclofenamate (n = 6) did not change RBF, while MAP decreased by 15 mmHg. A time-dependent significant enhancement of RBF autoregulatory efficiency was found in the drug-treated rats. Changes in renal function and reductions of prostanoid excretion in urine, of plasma renin activity, or serum aldosterone were similar in the nonsteroidal antiinflammatory drug groups. In conclusion, our findings demonstrate important time-related adjustments of renal hemodynamics in male rats treated with indomethacin, especially with the lower dose (3 mg/kg body wt iv). The factor(s) responsible for the hemodynamic changes remains unknown.

[Atrial natriuretic factor: retrospective and perspectives]. / Le facteur auriculaire natriurétique: rétrospective et perspectives.

Since the hypotensive and natriuretic properties of crude cardiac extracts were first demonstrated in 1981 in the rat, the effector molecule has been isolated, purified and synthesized. The hormonal factor is produced by atrial myocytes in mammals and stored as a prohormone. Secretion mainly results from a volemic stress inducing an atrial stretch. Secretion includes a maturation step. A peptide of 28 amino-acids (ANP) is then released into the bloodstream. ANP has a half-life of a few minutes. ANP binds to specific receptors expressed at the target cell surface. B-receptors mediate the biological actions of ANP by an increase in cGMP while C-receptors are involved in clearance of the peptide. The kidney as well as the cardiovascular and endocrine systems are the main target sites for ANP. The renal effects of ANP are expressed by an enhanced diuresis and natriuresis which may result from an increased glomerular filtration rate and/or a reduced tubular reabsorption of salt and water. Renal hemodynamics may also be modified due to a renal specific vasodilator effect of ANP. The reduction of systemic blood pressure may result from changes in cardiac output and/or in peripheral vascular resistance. Several neurohumoral interactions of ANP also contribute to sustain the cardiovascular and renal effects described above. In view of these properties, ANP is of particular interest in order to understand the homeostasis of salt and water under physiological as well as or physiopathological conditions. In this regard, therapeutic prospects are intensively investigated. Finally, evolutionary perspectives are actually considered from studies in lower vertebrates.

[Atrial natriuretic factor and water-sodium homeostasis: concepts and perspectives]. / Le facteur auriculaire natriurétique et l'homéostasie hydro-sodée: concepts et perspectives.

The discovery of an endocrine activity of the heart in 1981 was fundamental in order to understand the regulation of the effective circulatory volume. Indeed, the hormone which is secreted by the atrial cells (ANF) when these are distended suddenly in the presence of an enhanced preload of the heart, acts very rapidly upon the kidneys and the vasomotor tone. Its action restores without delay the effective circulatory volume following the renal elimination of an appropriate fraction of salt and water and attenuates the pressor effects of the increased intravascular volume. In this regard, the hormone is an emergency mediator. ANF may also be a long-term regulator of salt and water homeostasis by modulating the renal excretion of sodium. Finally, its role in pathological conditions such as congestive heart failure or essential hypertension remains to be elucidated. Nevertheless, interesting therapeutic perspectives may be considered, based on the unusual inactivation of ANF by clearance receptors.

[Regulation of kidney hemodynamics. Role of endothelial factors]. / La régulation de l'hémodynamique du rein. Le rôle des facteurs endothéliaux.

The vascular endothelium produces relaxing (PGI2 and EDRF) and contracting (endothelin) factors of the vascular smooth muscle cells. Among these, EDRF, recently identified as NO, is most important. Indeed, NO is continuously formed in the endothelial cells and can thus maintain a state of active and permanent vasodilatation. Consequently, NO may also set the systemic arterial pressure. Our experimental observations suggest that NO sets approximately 50% of the vasomotor tone of the arterial circulation including the renal circulation. In this regard, the activity of NO is not indispensable to renal blood flow autoregulation. Alterations of NO's and/or other endothelial factors' synthesis occur in a variety of cardio-vascular and renal diseases. A better understanding of the physiology and pathophysiology of the vascular endothelium will certainly allow to consider new and exciting therapeutic perspectives in these areas.

Effects of the diuretic torasemide on p-aminohippuric acid transport in the rat.

The effect of torasemide, a new diuretic, on p-aminohippuric acid (PAH) transport (TPAH) was studied using renal clearance and micropuncture techniques in anaesthetized rats. In clearance experiments, TPAH and TPAH/glomerular filtration rate (GFR) did not significantly change after i.v. administration of torasemide or furosemide but decreased after probenecid injection. In order to enhance the possibility to demonstrate torasemide and PAH interference, small volumes of [3H]-PAH + [14C]-inulin solutions were directly injected into the peritubular capillary system using calibrated micropipettes. When the concentration of microinjected PAH was less than or equal to 0.6 mmol/l, fractional recovery of [3H]-PAH from the micropunctured kidney was not significantly decreased by the diuretics in contrast to probenecid. When the concentration of microinjected PAH was greater than or equal to 5 mmol/l, fractional recovery of [3H]-PAH from the micropunctured kidney was significantly decreased by torasemide from 252% (control) to 210% (P less than 0.005), by furosemide to 217% (P less than 0.005), and by probenecid to 205% (P less than 0.01). Under these conditions, differential transit times between [3H]-PAH and [14C]-inulin in the micropunctured kidney were decreased from -15 to -4 s in the presence of torasemide (P less than 0.05). They were slightly but not significantly reduced by furosemide and probenecid. These findings suggest interference, at least to some extent, between torasemide and PAH secretion in the rat kidney.

Transmammary passage of cefoxitin: additional results.

It has been shown previously that cefoxitin was not detectable in the milk following an intramuscular injection of 1 Gm to mothers. In the present study, using a more sensitive HPLC method, we have shown in five women that low concentrations of cefoxitin (0.25 to 0.65 micrograms/ml) are measured in the milk after the intramuscular injection of 2 Gm.

Comparative multiple dose kinetics of two formulations of indomethacin.

The kinetics of a controlled release (CR) formulation of indomethacin 75 mg (Indocid-Retard) given once daily was compared with a conventional 25 mg indomethacin capsule (Indocid) given 3 times daily for 7 days, to 14 healthy volunteers, using a randomized, cross-over, multiple-dose study design. The following differences in plasma indomethacin profiles after the 2 treatments were observed: average peak concentrations (Cmax) for the CR regimen were higher and the time to peak (Tmax) was significantly delayed. Trough (pre-morning dose) plasma concentrations (Cmin) on Days 2, 5, 6 and 7 were significantly lower after the CR-formulation. No statistically significant differences between preparations for area under the plasma concentration time curve (AUC0-24 h) or for renal clearance were observed. Average steady-state plasma concentrations (Cssp) on Day 7 of the multiple dose regimens averaged 0.477 and 0.427 microgram/ml for the 75 mg CR once daily and the conventional 25 mg t.i.d. treatments, respectively. These results show that the bioavailability of the CR and conventional indomethacin formulations under these multiple-dose conditions was not significantly different.

Glucose transport in chronically altered rat nephrons.

Microinjection experiments were performed in anesthetized rats to study the tubular absorptive capacity for glucose (TG) in normal and chronically altered tubules, i.e., tubules that sustained anatomical repair and compensatory changes of their previously normal configuration after acute damage. TG was complete when the glucose load injected in normal or altered early or late proximal convolutions was less than or equal to 1.5 or less than or equal to 10 pmol . s-1, respectively. In normal tubules, TmG was 10 and 5 pmol . s-1 after early and late proximal microinjections, respectively. After early proximal microinjections in altered tubules, different levels of TmG were found. They related to the degree of compensatory growth. TmG was approximately 12, 24, or 35 pmol . s-1, respectively, in altered tubules with minor, moderate, or major compensatory growth. After late proximal microinjections, TmG was 15 pmol . s-1. TG variability was greater in altered than in normal tubules. Correlation between structural and functional compensatory changes was thus demonstrated. Furthermore, an important, albeit latent, absorptive capacity for glucose of the proximal straight tubule was found.

A study of the transplacental transfer and the mammary excretion of cefoxitin in humans.

Cefoxitin is a new semisynthetic cephamycin derivative with broad bactericidal activities. In order to determine the extent of the transplacental transfer of cefoxitin, 35 pregnant women received 1 Gm cefoxitin intramuscularly 15 to 180 minutes before normal or Caesarean delivery. Cefoxitin was measured microbiologically in maternal blood (multiple-time samples), umbilical blood (one-time sample), and amniotic fluid in the cases of Caesarean sections. The mammary excretion of cefoxitin injected at the same dose was investigated by measuring cefoxitin in the milk of 16 nursing mothers. In the maternal blood, a peak plasma level of approximately 25 microgram/ml was reached 30 minutes after the 1-Gm intramuscular injection. A clear-cut passage of cefoxitin in the umbilical cord blood was demonstrated. In the fetal blood, a peak level of 15 microgram/ml was obtained 45 minutes after the injection. No cefoxitin was detectable in any of the milk samples from 30 minutes to 24 hours after the 1-Gm intramuscular injection.