Biomedical subjects

R D Perrone

Publications and source records attributed to R D Perrone.

30 records · Page 2Linked to original sources

PubMed1990

Utility of radioisotopic filtration markers in chronic renal insufficiency: simultaneous comparison of 125I-iothalamate, 169Yb-DTPA, 99mTc-DTPA, and inulin. The Modification of Diet in Renal Disease Study.

Assessment of glomerular filtration rate (GFR) with inulin is cumbersome and time-consuming. Radioisotopic filtration markers have been studied as filtration markers because they can be used without continuous intravenous (IV) infusion and because analysis is relatively simple. Although the clearances of 99mTc-diethylenetriamine-pentaacetic acid (DTPA), 169Yb-DTPA, and 125I-iothalamate have each been compared with inulin, rarely has the comparability of radioisotopic filtration markers been directly evaluated in the same subject. To this purpose, we determined the renal clearance of inulin administered by continuous infusion and the above radioisotopic filtration markers administered as bolus injections, simultaneously in four subjects with normal renal function and 16 subjects with renal insufficiency. Subjects were studied twice in order to assess within-study and between-study variability. Unlabeled iothalamate was infused during the second half of each study to assess its effect on clearances. We found that renal clearance of 125I-iothalamate and 169Yb-DTPA significantly exceeded clearance of inulin in patients with renal insufficiency, but only by several mL.min-1.1.73m-2. Overestimation of inulin clearance by radioisotopic filtration markers was found in all normal subjects. No differences between markers were found in the coefficient of variation of clearances either between periods on a given study day (within-day variability) or between the two study days (between-day variability). The true test variability between days did not correlate with within-test variability. We conclude that the renal clearance of 99mTc-DTPA, 169Yb-DTPA, or 125I-iothalamate administered as a single IV or subcutaneous injection can be used to accurately measure GFR in subjects with renal insufficiency; use of the single injection technique may overestimate GFR in normal subjects.

Creatinine↗

PubMed1990

Aldosterone induces apical vesicles in rat distal colon.

Mineralocorticoid steroids markedly alter ion transport in responsive epithelia. Increases in absorption of Na+ and secretion of K+ and H+ are accompanied by increases in surface area of the basolateral membrane. The basolateral membrane changes are associated with increased Na(+)-K(+)-ATPase activity and increased numbers of Na(+)-K(+)-ATPase pump sites. It is thought that H+ secretion is mediated by H+ pumps contained in apical vesicles that are added to the luminal membrane in response to acidifying stimuli. Whether there are changes in the number or volume of apical vesicles in response to aldosterone has not been evaluated. To this purpose, we evaluated apical membrane morphology in rat distal colon, a mineralocorticoid-responsive epithelium. We found that aldosterone infused for 4-7 days by osmotic minipump significantly increased the number, surface density, and total volume of apical vesicles. Exposure of tissues to 5% CO2 for 15 min before fixation resulted in significant decreases in vesicle number, surface density, and volume in aldosterone-stimulated tissues. After CO2, apical vesicles in aldosterone-stimulated tissues tended to be closer to the luminal membrane; apical membrane surface density was increased but not to a significant degree. Fluorescence microscopy demonstrated acridine orange accumulation in discrete points under the lumen, suggesting the presence of acidic vesicles in this location. We propose that aldosterone increases the activity of a membrane shuttle system that is regulated by CO2 as found in other H(+)-secreting epithelia. This system may mediate aldosterone-induced changes in colonic H+ transport.

Aldosterone↗

PubMed1989

Cyst function in polycystic kidney disease: nongradient cysts.

Previous studies from this laboratory have demonstrated active sodium transport by cyst epithelia obtained from human polycystic kidneys. Cysts which maintained a steep sodium gradient between cyst fluid and plasma (gradient cysts) exhibited conductive amiloride sensitive sodium transport. Cysts which failed to maintain a sodium gradient between cyst fluid and plasma (nongradient cysts) were insufficiently characterized. In the present study, we report flux and electrical parameters of 23 nongradient cysts studied in vitro. Nongradient cysts exhibit low PD, low Isc, and high conductance. Unidirectional fluxes of sodium and chloride varied from approximately 14.4 to greater than 250 microEq.h-1.cm-2 and net flux was not significantly different from zero. There was no apparent effect on flux or electrical parameters of amiloride, ouabain, acetazolamide, or bumetanide. There was a very high correlation between unidirectional flux of sodium and chloride in individual cysts which was similar to the predicted relationship for diffusional fluxes. This correlation suggested that movement of sodium and chloride across cyst membranes was passive via an aqueous channel. Estimates of ionic permeability exceeded those determined for proximal nephron by almost one order of magnitude. We conclude that nongradient cysts are nonfunctional and, regardless of their origin, do not function analogously to the proximal nephron.

Absorption↗

PubMed1988

Serum creatinine and renal function.

Serum creatinine is widely interpreted as a measure only of renal function; however, the serum level reflects not only renal excretion, but also the generation, intake, and metabolism of creatinine. In this review, we demonstrate that serum creatinine does not provide an adequate estimate of glomerular filtration rate (GFR), and contrary to recent teachings, that the slope of the reciprocal of serum creatinine vs time does not permit an accurate assessment of the rate of progression of renal disease. In clinical investigation, it is essential to utilize more accurate and sensitive measures of renal function to estimate GFR and progression. As effective treatments for progressive renal diseases are discovered, it will also be necessary to employ these measurements in clinical practice.

Creatinine↗

PubMed1988

Aldosterone and PCO2 enhance rubidium absorption in rat distal colon.

Recent studies of rabbit colon have indicated the presence of a vanadate-sensitive K+-dependent proton pump, suggesting the existence of an H+-K+-ATPase. The participation of such a mechanism for colonic K+ absorption in the rat has not been determined. To this purpose, we attempted to detect the presence of pH-linked mechanisms for K+ absorption in rat distal colon using 86Rb as a marker for K+. We found that Rb+ absorption in Na-Ringer directly correlated with the in vitro partial pressure of CO2 (PCO2) in aldosterone-stimulated but not in control rats. Similar studies performed using Na-free Ringer demonstrated that PCO2 markedly augmented Rb+ absorption in both control and aldosterone-stimulated rat colon. Rb+ absorption was inhibited by orthovanadate, SCH28080, and mucosal ouabain in Na-free Ringer, but there was no effect of omeprazole, furosemide, or bumetanide. Barium applied to the serosa was also effective in inhibiting Rb+ absorption, suggesting that Rb+ exit from the cell was conductive. These findings are consistent with the presence of an active K+ pump that is activated by pretreatment with aldosterone and increased in vitro PCO2 and that is inhibited by orthovanadate, SCH28080, and mucosal ouabain. The constellation of findings suggests that participation of an ATPase that is not typical of either Na+-K+-ATPase or H+-K+-ATPase.

Acetazolamide↗

PubMed1987

Biphasic 19-nor-deoxycorticosterone excretion after adrenal enucleation is associated with altered adrenal mitochondrial cytochrome P450 11 beta-, 18-, and 19-hydroxylase activities.

After adrenal enucleation (AE) rats avidly retain sodium (early phase), but after 7-10 days they lose this sodium avidity (late phase). Although increased production of a mineralocorticoid, 19-nor-deoxycorticosterone (19-Nor-DOC), has been implicated, 19-Nor-DOC levels during the early and late phases of AE have not been systematically measured. Furthermore it is not known why 19-Nor-DOC production should increase during a time when production of 11 beta- and 18-hydroxylated corticosteroids are decreased in AE. The purpose of this study was to examine the 11 beta, 18-, and 19-hydroxylase pathways in the early and late phases of AE. The results demonstrate increased urinary 19-Nor-DOC and decreased 18-OH-DOC and corticosterone excretion in the early phase of AE at a time when adrenal mitochondrial 11 beta- and 18-hydroxylase activities were decreased but 19-hydroxylase activity was unchanged. During the late phase of AE, urinary 19-Nor-DOC had decreased and 18-OH-DOC and corticosterone had increased to levels indistinguishable from those in sham controls. This reduction in 19-Nor-DOC was associated with a decrease in 19-hydroxylase activity in AE. Since the 11 beta, 18-, and 19-hydroxylases have a common substrate (DOC), it is possible that differential flux of DOC through these pathways could account for the changes in steroid production in AE. These data suggest that the increased 19-Nor-DOC excretion in AE may be due to alterations in enzyme activity leading to a shunting of DOC into the 19-Nor-DOC pathway. In addition, the synchronicity of 19-Nor-DOC with sodium excretion suggests that it has an important role in the pathogenesis of the sodium retention in AE.

Adrenal Glands↗

PubMed1986

Sodium retention after adrenal enucleation.

Adrenal enucleation (removal of the adrenal gland, leaving the capsule intact) results in regeneration of the adrenal cortex. During the first 1-2 wk of adrenal regeneration, marked renal sodium avidity and positive sodium balance are noted. This renal sodium avidity appears mediated via adrenocorticotropin-stimulated secretion of a potent mineralocorticoid by the regenerating adrenal cortex. In this review, we have examined relationships between the histology and ultrastructure of the regenerating adrenal cortex, renal sodium handling, and adrenal steroid production at various times after the initiation of adrenal regeneration. Plasma levels of known mineralocorticoids are subnormal during the period of most intense sodium avidity, while urinary excretion of a potent mineralocorticoid, 19-nordeoxycorticosterone, has been found to be increased in rats with regenerating adrenals during this period of most intense sodium avidity. This hormone, however, is not elevated in rats with regenerating adrenals after resolution of the period of sodium avidity. In this article, we review the experimental evidence regarding the potency of this mineralocorticoid and its likely role in the sodium retention after adrenal enucleation.

Adrenal Glands↗

PubMed1985

In vitro function of cyst epithelium from human polycystic kidney.

It is thought that cysts in polycystic kidneys originate from nephron segments and function in a manner similar to the segment or origin. The indirect evidence for this derives from studies of microanatomy and cyst fluid composition. Cysts with low Na+ have been classified as distal, whereas cysts with high Na+ have been classified as proximal. In order to directly determine the transport characteristics of cyst epithelium, cysts from a human polycystic kidney were studied in vitro using Ussing chamber techniques. Composition of cyst fluid was determined in parallel with these studies. Cysts with low Na+ (gradient cysts) demonstrate characteristics consistent with distal nephron origin including elevated potential difference (PD), short-circuit current (Isc), and low conductance. PD and Isc of gradient cysts were amiloride sensitive. Nongradient cysts, however, require additional characterization. At least two types of nongradient cysts were identified, one with characteristics consistent with proximal nephron origin and another apparently without function. These studies are the first direct evidence for active transport of cysts from human polycystic kidney and provide strong evidence to support the concept that cysts function in the same manner as the nephron segment of origin.

Amiloride↗

PubMed1984

Effect of aldosterone and dexamethasone pretreatment on sodium transport in rat distal colon in vitro.

Aldosterone and dexamethasone stimulate sodium absorption in the rat colon in vivo. In vitro, increased amiloride inhibitable short-circuit current (ISC) has been demonstrated following aldosterone or dexamethasone treatment. Since ISC bears no relationship to sodium flux (JNa) in the untreated rat colon, we measured JNa in partially stripped voltage clamped segments of rat distal colon. Our results demonstrate directly that continuous infusion of aldosterone or dexamethasone for 4-7 days stimulated amiloride inhibitable JNa by stimulating JNaM -S. The amiloride inhibitable portion of JNaM -S was highly correlated with and approximately equal to the amiloride inhibitable ISC. Amiloride had no effect in controls. We conclude that JNaM -S in the rat distal colon is only sensitive to mucosal amiloride after treatment with aldosterone or dexamethasone. The amiloride sensitive ISC in these treated tissues was a good measure of the amiloride sensitive JNa. Small differences between aldosterone and dexamethasone treatment were noted in the effect on transepithelial resistance, potential difference, and the ISC after amiloride.

Aldosterone↗

PubMed1984

Suppression of coupled Na-Cl absorption by aldosterone and dexamethasone in rat distal colon in vitro.

Basal Na absorption in the rat colon is coupled to that of Cl in an electroneutral fashion. We previously determined that aldosterone or dexamethasone induces amiloride-sensitive mucosal-to-serosal Na flux approximately equal to the amiloride-sensitive short-circuit current in rat distal colon in vitro. However, the effect of these steroids on coupled Na-Cl absorption was not examined. For this purpose, we determined the unidirectional flux of Na and Cl in voltage-clamped distal colon segments from rats treated with aldosterone or dexamethasone. Amiloride was used as a probe for conductive Na absorption, and acetazolamide and Cl-free solutions were used as probes for coupled Na-Cl absorption. Our results indicate that the nature of colonic Na absorption is markedly changed after treatment with these steroids. In contrast to findings in the untreated rat, colonic Na absorption after treatment with aldosterone or dexamethasone was largely independent of the presence of Cl. Net Cl absorption and acetazolamide sensitivity were both greatly diminished. Thus, aldosterone and dexamethasone have multiple effects on Na transport in rat distal colon. In addition to the stimulation of conductive Na absorption by aldosterone, an effect well described in other epithelia, there is marked suppression of coupled Na-Cl absorption. Dexamethasone was less effective in suppressing Cl absorption but equally effective in stimulating conductive Na absorption. These steroid effects were greater in the terminal 1-2 cm of the rat colon.

Acetazolamide↗

PubMed1982

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↗

PubMed1981

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↗