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H H Bengele

Publications and source records attributed to H H Bengele.

At least 37 records · Page 2Linked to original sources

Mineralocorticoid activity of 19-nor-DOC and 19-OH-DOC in adrenalectomized rat.

Excess mineralocorticoid activity is thought to be responsible for the increased sodium reabsorption found after adrenal enucleation, but no known mineralocorticoid has been demonstrated in quantities sufficient to account for this antinatriuresis. 19-Hydroxydeoxycorticosterone (19-OH-DOC) has been synthesized by the incubated enucleate adrenal capsule and 19-nordeoxycorticosterone (19-nor-DOC), a possible metabolite, has been found in the urine of rats with regenerating adrenal glands. To evaluate the in vivo mineralocorticoid potency of these steroids, we studied glucocorticoid-replete adrenalectomized rats and measured the sodium and potassium excretion after administration of these steroids. Our results indicate that 19-nor-DOC has equipotent antinatriuretic activity compared to aldosterone but was less kaluretic. 19-OH-DOC had no significant antinatriuretic or kaluretic activity. We conclude that 19-nor-DOC is a potent mineralocorticoid and may be responsible for the enhanced sodium reabsorption found after adrenal enucleation.

Adrenalectomy↗

Effect of adrenal enucleation on inner medullary collecting duct function in the rat.

After adrenal enucleation rats have an impaired ability to excrete a salt load. From micropuncture studies comparing data obtained from the late distal collection site and the urine, it has been suggested that this antinatriuretic effect occurs along the collecting duct. These studies are indirect, however, and cannot evaluate the contribution of deep nephrons. We have performed studies directly measuring inner medullary collecting duct (IMCD) function in saline-loaded rats 6 days after adrenal enucleation (AE). The fraction of filtered fluid, sodium, chloride, and potassium was analyzed as a function of IMCD length. In six AE rats 35% of the fluid, 35% of the sodium, and 31% of the chloride delivered to the IMCD was reabsorbed. In six saline-loaded control rats, however, no statistically significant net reabsorption of fluid sodium, or chloride was detected. Net potassium secretion along the IMCD was found in both AE and control rats. No difference between groups was noted, and net addition accounted for 17% of the potassium excreted. We conclude that after AE, the excretion of fluid, sodium, and chloride is impaired during saline expansion because of enhanced reabsorption along the IMCD. AE does not affect potassium handling along the IMCD or potassium excretion.

Adrenal Glands↗

Renal function in the term pregnant rat: a micropuncture study.

The purpose of this study was to define individual nephron function and salt and fluid reabsorption in the term pregnant rat utilizing standard micropuncture techniques. The studies were performed at the time of maximal sodium retention and when extracellular fluid volume was significantly increased. During micropuncture in 7 pregnant and 9 non-pregnant rats, we found no difference, respectively, in GFR 1.04 +/- 0.06 vs. 1.13 +/- 0.06 ml/min/kidney or nephron GFR 35 +/- 0.9 vs. 33 +/- 1 ml/min. Fractional and absolute Na reabsorption was also not significantly different in the proximal tubule or the loop of Henle. Along the distal tubule, fractional reabsorption was higher in pregnancy, 71 +/- 3 vs. 62 +/- 4 but not statistically different, 0.05 less than p less than 0.10. Beyond the late distal tubule absolute delivery and reabsorption were greater in the nonpregnant rats. Distal nephron potassium secretion was similar in both groups. In anesthetized rats during clearance studies but without surgery for micropuncture, GFR in the pregnant group was significantly higher than the nonpregnant rats, 1.65 +/- 0.06 vs. 1.28 +/- 1.10 ml/min/kidneys as was tubular reabsorption of sodium. We conclude that pregnant rats exhibit glomerular tubular balance and that potassium handling along the superficial nephron is unaffected by pregnancy. The sodium retention of pregnancy appears to occur because of the failure of inhibition of tubular sodium reabsorption, a response which is normally expected when extracellular volume is expanded.

Animals↗

Mineralocorticoid activity of 19-nor-DOC and 19-OH-DOC in toad bladder.

Adrenal enucleation is followed by a period of increased sodium reabsorption thought to be due to excess mineralocorticoid activity. However, it has not been demonstrated that increased production of any known mineralocorticoid accounts for this antinatriuresis. Recently, 19-hydroxydeoxycorticosterone (19-OH-DOC) was found in incubates of regenerating adrenal capsules 3-4 days postenucleation and 19-nordeoxycorticosterone (19-nor-DOC) was identified in the urine of rats with regenerating adrenals. Because it was possible that these hormones might play a role in the sodium retention after adrenal enucleation, we compared the mineralocorticoid activity of these steroids to aldosterone using the toad bladder. Using short-circuit current as a measure of sodium transport, we found that 19-OH-DOC (10(-8) M) had no significant effect on sodium transport. However, 19-nor-DOC (10(-8) M) increased sodium transport to a degree not different from aldosterone (10(-8) M). Furthermore, the onset of action, duration of activity, and inhibition of effect of 19-nor-DOC by spironolactone were not different from that of aldosterone. We conclude that 19-nor-DOC exhibits a significant effect on sodium transport and thus has the potential to play a role in the sodium retention following adrenal enucleation. Under the conditions of these studies, 19-OH-DOC exhibited no effect on sodium transport.

Aldosterone↗

Role of aldosterone in sodium retention of pregnancy in the rat.

The purpose of this study was to test whether the absence or inhibition of aldosterone would alter the Na retention of pregnancy in the rat. We performed metabolic balance studies during the last 2 wk of the 3-wk rat pregnancy in the following four groups of saline-drinking rats: nonpregnant, sham adrenalectomized; pregnant, sham adrenalectomized; nonpregnant, adrenalectomized; and pregnant, adrenalectomized. Significant net Na retention was not found during the 2nd wk in any of the groups. During the final week, however, both pregnant groups retained between 8 and 11 meq Na more than their respective control groups. In addition, we measured plasma aldosterone concentration in these rats at term. The mineralocorticoid was not detectable in the nonpregnant adrenalectomized rats but was present in the pregnant adrenalectomized rats at a concentration of about 50% of that found in the pregnant sham-adrenalectomized rats. Serial measurements revealed that aldosterone was measurable by day 18 and nondetectable by 2 days postpartum in these pregnant adrenalectomized rats. Comparable balance studies were also performed in three groups of water-drinking rats: nonpregnant, pregnant, and pregnant rats that received large daily doses of spironolactone. During the 3rd wk both pregnant groups were in significant positive Na balance. Net Na retention for untreated pregnant rats was 8.4 meq and for the spironolactone treated, 6.9 meq, values that were not significantly different. We conclude that is is unlikely that aldosterone plays a critical role in the Na retention found during rat pregnancy.

Adrenal Glands↗

Urinary concentrating defect in the aged rat.

The renal concentrating ability of Fischer 344 rats was studied at 23 and 4 mo of age. Maximum urine concentration after 40 h of dehydration with or without vasopressin injection was significantly lower (P less than 0.01) in old (2,550 +/- 70 and 2,363 +/- 107 mosmol/kg H2O2, respectively) vs. young (3,242 +/- 50 and 3,162 +/- 50 mosmol/kg H2O, respectively) rats. Free water reabsorption (TcH2O/GFR) rose progressively as a function of osmolar clearance, and at similar values of distal solute delivery TcH2O was clearly reduced in the old group. Free water formation (CH2O/GFR) rose linearly as a function of urine flow and was not different between old and young rats. Glomerular filtration rate was also not different between age groups under the conditions studied. Nonurea (sodium + potassium + ammonium) x 2 and urea solute concentrations as well as total calculated osmolality in the cortex, outer medulla, or inner medulla were not different between age groups. Because the indices of ascending limb solute delivery and transport and the solute gradient for water reabsorption were similar, we conclude that the concentrating defect in aged rats is most likely secondary to a decrease in water permeability along the collecting duct.

Absorption↗

pH and PCO2 profiles of the rat inner medullary collecting duct.

To directly characterize acidification by the collecting duct, we developed pH and PCO2 microelectrodes suitable for microcatheterization of the inner medullary collecting duct (IMCD). In saline-infused control rats apparent in situ pH fell significantly along the IMCD, from 5.95 at 60% length to 5.49 at the papilla tip. Luminal PCO2 averaged 34 +/- 1 mmHg and PD averaged +3 mV. In rats acutely infused with 0.1 N HCl, apparent in situ pH also decreased significantly from 5.56 to 5.28, PD averaged +2 mV, and luminal PCO2 31 +/- 1 mmHg. The luminal PCO2 of HCl-infused rats was significantly less than controls and both levels were significantly below arterial PCO2. Corroborating the in situ pH profiles, equilibrium pH measured on collected IMCD samples also decreased significantly with percent length. In samples measured in situ and at equilibrium, a small but significant acid disequilibrium pH ws seen in both groups. We interpret these results to indicate that the IMCD actively participates in distal acidification. It is proposed that acidification by the IMCD is predominantly mediated by hydrogen ion secretion which simultaneously acidifies luminal fluid and generates a cellular sink for CO2, thereby inducing an acid disequilibrium pH by two mechanisms.

Acidosis↗

Acute metabolic acidosis augments collecting duct acidification rate in the rat.

It is generally assumed that at least part of distal acidification occurs along the collecting duct. Complete and direct evaluation of acidification along this nephron segment is unavailable, however. The purpose of these experiments was to quantify the net acidification rate along the inner medullary collecting duct (IMCD) and to measure the effect of acute HCl acidosis. In 13 control rats (arterial pH, 7.39 +/- 0.01; PCO2, 39 +/- 1 mmHg) and 11 HCl-infused rats (arterial pH 7.18 +/- 0.01; PCO2, 40 +/- 1 mmHg) we obtained four to eight IMCD samples by a modified microcatheterization technique that also permitted measurement of in situ and in vitro pH. Tubular fluid pH decreased along the IMCD in both groups and was more acidic by 0.2-0.4 pH units in the acid-infused rats. Bicarbonate reabsorption was noted in both groups as delivery along the IMCD decreased from 205 +/- 127 to 26 +/- 6 nmol/min in control rats and from 219 +/- 118 to 17 +/- 4 nmol/min in the acidotic group. Ammonia delivery to and addition along the IMCD was significantly greater in the acidotic rats--from 193 +/- 59 to 462 +/- 53 nmol/min in control and from 887 +/- 126 to 1,396 +/- 90 nmol/min in acidotic rats. No significant change in total or titrated phosphate was seen. Net acid addition along the IMCD was over twice as great in acidotic rats, 450 vs. 970 nmol/min. Our results indicate that significant net acid addition occurs along the IMCD and that during acidosis this acidification rate increases.

Acid-Base Equilibrium↗

Impaired natriuresis after volume expansion in the aged rat.

These experiments were designed to compare the natriuretic ability of old(age 22-24 months) and young (4-6 months) rats after volume expansion. No difference in extracellular fluid volume was noted as estimated by inulin space; old 18.8 +/- 0.6% and young 18.2 +/- 0.7% of body weight. Standard clearance techniques were utilized in unanesthetized animals. The fraction of infused sodium excreted during and after expansion with isotonic saline equal to 7% BW was statistically lower in the old group 53 +/- 2 vs. 68 +/- 3% (p less than 0.01). Similar measurements were made during the infusion of whole blood equal to 2.3% BW. Again the old rats excreted a significantly lower fraction of the infused Na, 55 +/- 10 vs. young 112 +/- 12%. These differences do not appear to be explained by changes in glomerular filtration rate, blood pressure, hematocrit or serum protein concentration. We conclude that aged rats have an impaired ability to excrete sodium with volume expansion but the mechanism for this defect is yet to be determined.

Age Factors↗

Renal hemodynamics and volume homeostasis during pregnancy in the rat.

We believe that in pregnant rats, GFR is elevated at term, whereas renal plasma flow appears not to be increased. The mechanism for this increment is unclear, as is the specific time during gestation when renal hemodynamics increase. Rats increase their salt appetite and significantly positive sodium balance occurs, which is most pronounced during the last week of gestation. The retained sodium is distributed in part to the products of conception and in part to the mother, particularly in increasing her extracellular fluid volume. Although chronic volume expansion is present, absolute tubular sodium reabsorption remains elevated. The mechanism for this elevated tubular reabsorption appears no to be related to aldosterone because reduction or inhibition of this mineralocorticoid does not affect sodium balance significantly.

Aldosterone↗

Sodium balance after adrenal enucleation.

To better define the relationship between adrenal enucleation (AE), sodium retention and adrenal regeneration hypertension (ARH), we measured daily sodium balance in rats after bilateral adrenal enucleation with (AEN) and without uninephrectomy (AE), and before and after development of ARH, along with the appropriate control groups. We found that both AE and AEN groups retained sodium during 7 days after surgery; AE 1.16 +/- 0.24 and AEN 1.32 +/- 0.33 meq/100 g body wt. Sham-operated, uninephrectomized rats and AE rats treated with spironolactone were in zero sodium balance. In the AEN rats after the development of ARH (BP greater than 150 Torr), zero sodium balance was also noted. Only AEN rats developed hypertension while sham-operated, uninephrectomized rats and AE rats with both kidneys remained normotensive for 28 wk. In summary, we have demonstrated that for 1 wk after AE, rats are in positive sodium balance and this is reversed by spironolactone but not by uninephrectomy.

Adrenal Medulla↗

Sodium balance during pregnancy in the rat.

The purpose of this study was to quantitate sodium balance during gestation in the rat (3 wk) to determine the time course of salt retention and to define the distribution of the retained salt. We have found that while sodium retention appears to begin during the 2nd wk, the bulk of retention occurs during the 3rd wk when the rat excretes only 67% of that ingested. Compared to that of nonpregnant, control rats, net retention for all of gestation was 9.8 meq. Despite a significantly higher sodium intake in pregnant rats, neither urinary nor fecal sodium excretion was different in pregnant and control rats. Fifty-nine percent of the retained sodium was found in the products of conception. Inulin space was increased by term from 19.7 to 25.4% of nonconceptus body weight. In pregnant rats a net retention of 6.3 meq of potassium was noted, 55% of which was found in the products of conception. We conclude that the rat retains sodium and potassium during pregnancy, predominantly in the third trimester. Over half of these salts are found within the conceptus products.

Animals↗

Sodium and chloride transport along the inner medullary collecting duct: effect of saline expansion.

The effect of volume expansion on inner medullary collecting duct (IMCD) sodium transport remains controversial. Studies employing micropuncture of the IMCD base and tip were interpreted to demonstrate enhanced sodium and chloride reabsorption. Data obtained by microcatheterization evaluating only sodium transport revealed either no reabsorption or net addition. We have examined both sodium and chloride transport by microcatheterization. Volume expansion was comparable to the micropuncture studies: 0.9% saline equal to 10% body wt and then matched to urine flow. The fraction of filtered fluid, sodium, and chloride was analyzed as a function of IMCD length. In eight hydropenic rats 60% of the fluid, 71% of the sodium, and 48% of the chloride delivered to the IMCD was reabsorbed. In six volume-expanded rats no significant net reabsorption of fluid, sodium, or chloride was found. Accordingly, in contrast to the micropuncture results, we have demonstrated that net sodium chloride and fluid reabsorption are absent during volume expansion. We conclude that during volume expansion, fluid, sodium, and chloride excretion increase, in part, because of a reduction in net reabsorption along the IMCD. The degree of volume expansion does not account for the discrepancy between the two techniques.

Adsorption↗

Calcium and magnesium transport along the inner medullary collecting duct of the rat.

We have measured calcium and magnesium transport along the inner medullary collecting duct (IMCD) in rats by the microcatheterization technique. The fraction of filtered divalent cation ((F/P)Ca,Mg/In) as a function of IMCD length was analyzed by linear regression. In eight control rats calcium reabsorption was demonstrated, inasmuch as there was a significant correlation and slope, P less than 0.001. (F/P)Ca/In decreased from 2.2 +/- 0.3% at the beginning of the IMCD to 0,84 +/- 0.1% in the urine. (F/P)Mg/In was not changed along the IMCD, After acute thyroparathyroidectomy (TPTX) (F/P)Ca/In increased to 4.6 +/- 0.4% at the beginning of the IMCD and 1.55 +/- 0.1% in the urine. The slope was not significantly different from the control group. (F/P)Mg/In was unchanged and was not different from the control group. Accordingly, net Ca reabsorption occurs along the IMCD and the fractional Ca reabsorption is not altered by TPTX. Net Mg transport along the IMCD was absent in both control and TPTX rats; The increased calciuresis after TPTX is not dependent on IMCD function nor is Mg excretion under the conditions studied.

Animals↗

Potassium secretion along the inner medullary collecting duct.

Potassium transport along the inner medullary collecting duct (IMCD) was evaluated by the microcatheterization technique in Charles River CD (cesarean derived) rats 7-9 days after sham operation (S) or uninephrectomy (UNPX). The fraction of filtered potassium (TF/P)K/In) as a function of IMCD length was analyzed by linear regression. In 13 S rats there was a significant correlation and slope (P less than 0.001) and (TF/P)K/In increased from 14% at the beginning of the IMCD to 25% in the urine. IMCD potassium secretion accounted for about half of the excreted potassium. In the UNPX rats a significant correlation and slope was also obtained (P less than 0.001); (TF/P)K/In at the beginning of IMCD was 24% and increased to 36% in the urine. No difference in slope was noted between the groups. There was a slightly greater absolute potassium secretion after UNPX (0.77 +/- 0.03 S vs. 0.93 +/- 0.04 mueq/min UNPX), but this did not account for most of the difference in potassium excretion noted. We conclude that net potassium secretion occurs along the IMCD in S and UNPX rats. After UNPX, there is significantly greater potassium delivery to the IMCD and a greater kaluresis. The increased kaluresis cannot be accounted for primarily by increased potassium secretion along the IMCD.

Animals↗

Phosphate transport along the inner medullary collecting duct of the rat.

The question of phosphate transport along the collecting duct remains controversial inasmuch as no data from direct in vivo evaluation of this nephron segment have been reported. We measured net phosphate transport along the inner medullary collecting duct (IMCD) using the collecting duct microcatheterization technique in five groups of rats. In control rats no net phosphate transport was found and 9.4% of the fraction of filtered phosphate (FFP) entered the IMCD and was excreted. After acute thyroparathyroidectomy (TPTX) there was a striking reduction in the FFP entering the IMCD, 1.8%, and significant reabsorption occurred, 0.5% being excreted. With acute TPTX and parathormone infusion, delivery increased to 33% without significant change along the IMCD. With acute TPTX and phosphate infusion, delivery was increased to control levels but no change was found in net phosphate transport. In rats studied 5-7 days after uninephrectomy alone, phosphate delivery was greater than in control, 25%, and no net phosphate transport was found. These studies demonstrate that phosphate absorption occurs along the IMCD in acutely TPTX rats when the delivery of phosphate to the IMCD is markedly reduced. The increase in phosphaturia which occurs after a reduction in renal mass cannot be accounted for by changes in net phosphate transport along the IMCD.

Animals↗

Renal response to Ringer expansion in developing rats.

Male rats were studied between 20 and 60 days of age. Standard renal clearance techniques were used. The efficiency of the diuretic response, the sodium response, and the potassium response were calculated as defined previously. Results indicate that both diuretic and sodium efficiency is lower between the ages of 20 and 30 days as compared to 40 and 60 days of age, whereas potassium efficiency shows no age dependence. In morphological studies, it has been observed that the proximal tubule cells of 22-day-old rats show changes in lateral intercellular spaces with comparable features to those of mature animals. The spaces widened during volume expansion. The change is quantitatively the same as that found in mature rats. Both blood pressure and hematocrit show continuous increase with age. The response of Ringer infusion in both immature and mature animals may be a mixed response involving changes in physical factors and renal responses to volume expansion per se.

Age Factors↗