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Biomedical subjects

D C Batlle

Publications and source records attributed to D C Batlle.

At least 37 records · Page 2Linked to original sources
PubMed1990

Effect of cyclosporin A on renal function and kidney growth in the uninephrectomized rat.

This study was designed to characterize the effect of cyclosporin A (CsA) on renal function and compensatory kidney growth in a rat model of uninephrectomy (Ux). The infusion of CsA (12.5 mg/k body wt) after acute Ux resulted in a fall in glomerular filtration rate (GFR) and renal plasma flow (RPF) and a marked increase in renal vascular resistance (RVR). Three weeks following Ux, GFR was also reduced in CsA treated animals as compared to pair-fed controls (0.39 +/- 0.03 vs. 0.67 +/- 0.06 ml/min/100 g, P less than 0.001), but RPF was not (1.97 +/- 0.14 vs 2.19 +/- 0.34 ml/min/100 g). The reduction in GFR seen in rats treated with CsA was fully reversible two weeks after discontinuation of the drug. Three weeks after Ux, kidney weight in CsA-treated animals increased to the level of pair-fed controls (1.50 +/- 0.05 vs. 1.57 +/- 0.06 g) but renal cortical RNA (39.4 +/- 4.3 vs. 49.3 +/- 1.3 micrograms/ml, P less than 0.05), DNA (26.4 +/- 1.7 vs. 34.7 +/- 2.1 micrograms/ml, P less than 0.01), and protein content (6.4 +/- 0.3 vs. 7.8 +/- 0.2 mg/dl, P less than 0.001) were all markedly reduced. Unilateral renal denervation in CsA-treated rats resulted in an increase in GFR and RPF as compared to that of pair-fed sham-denervated animals also treated with CsA (0.57 +/- 0.06 vs. 0.39 +/- 0.03 ml/min/100 g, P less than 0.025 and 2.14 +/- 0.14 vs. 1.63 +/- 0.20 ml/min/100 g, P less than 0.025, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Cytosolic calcium in T lymphocytes from the spontaneously hypertensive rat.

To gain further insight into the possible generalized nature of intracellular calcium-related alterations in hypertension we measured free cytosolic calcium (iCa2+) in lymphocytes obtained from the spleen and the blood of the spontaneously hypertensive rat (SHR) and age-matched normotensive Wistar-Kyoto (WKY) rats. By monitoring Fura-2 fluorescence at an excitation wavelength of 340 nm and an emission wavelength of 510 nm we estimated; Ca2+. In peripheral lymphocytes from the SHR iCa2+ was increased as compared to those from WKY rats (146 +/- 14 and 112 +/- 6.0 nm, respectively, P less than .025). In contrast, in lymphocytes obtained from the spleen, iCa2+ was not different between SHR and WKY rats (93 +/- 7.0 and 96 +/- 8.0 nm, respectively). When spleen cells were subjected to selective B lymphocyte depletion to generate a preparation of predominantly T lymphocytes, iCa2+ was found to be higher in SHR than in WKY rats (149 +/- 23 and 89 +/- 12 nm, respectively, P less than .05). The finding that iCa2+ is elevated in peripheral lymphocytes and spleen cells subjected to B cell depletion but not in untreated spleen cells indicates that T, but not B, lymphocytes have increased iCa2+ in the SHR. This observation may be related to existing evidence that T lymphocyte function is impaired in the SHR. An increase in iCa2+ is not a phenomenon generalized to all cells of this model of genetic hypertension.

Animals↗
PubMed1990

Reduced intracellular pH in lymphocytes from the spontaneously hypertensive rat.

This study was designed to determine the cytoplasmic pH (pHi) profile of lymphocytes from a rat model of genetic hypertension that is well suited for study before and after the development of spontaneous hypertension. For this purpose, pHi was measured in thymic lymphocytes obtained from spontaneously hypertensive rats (SHR) and from age-matched Wistar-Kyoto (WKY) control rats using 2',7'-bis carboxyethyl-5,6-carboxyfluorescein (BCECF), a pH-sensitive fluorescence probe. At the age of 16-20 weeks, pHi of lymphocytes suspended in a HCO3-free HEPES-buffered solution, was markedly lower in the SHR than in the WKY rats (7.07 +/- 0.02, n = 16 and 7.22 +/- 0.01, n = 15, respectively, p less than 0.001), whereas systolic blood pressure was higher in SHR than in WKY rats (175 +/- 5.0 and 105 +/- 3.0 mm Hg, respectively, p less than 0.001). In rats less than 5 weeks of age, pHi was also lower in SHR than in WKY rat lymphocytes (7.12 +/- 0.04, n = 11 and 7.23 +/- 0.04, n = 11, respectively, p less than 0.05), although at this age systolic blood pressure was not different between the two groups (87 +/- 4.0 and 85 +/- 3.0 mm Hg, respectively). In lymphocytes suspended in a more physiological HCO3/CO2-buffered solution, pHi was again lower in the adult SHR than in the WKY rat (7.18 +/- 0.02, n = 16 and 7.31 +/- 0.02, n = 16, respectively, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1990

Kinetic properties of the Na+/H+ antiporter of lymphocytes from the spontaneously hypertensive rat: role of intracellular pH.

Enhanced activity of the Na+/H+ antiporter is increasingly reported as a feature of cells from hypertensive subjects but the intracellular pH (ipH) dependency of its activity has not been examined. This study was designed to characterize the kinetic properties of the Na+/H+ antiporter in lymphocytes from adult spontaneously hypertensive rats (SHR) and in those from age-matched normotensive Wistar-Kyoto (WKY) controls. Steady-state ipH, estimated from the measurement of BCECF fluorescence, was significantly lower in lymphocytes from the SHR than in those from WKY rats (7.09 +/- 0.02, n = 17 and 7.17 +/- 0.03, n = 19, respectively, P less than 0.025). The velocity of the antiporter determined from the product of the change in intracellular hydrogen ion concentration (i[H+]) by the buffering power measured concurrently at each starting ipH exhibited similar kinetic parameters in SHR and WKY cells: Vmax, 72 +/- 18 vs. 79 +/- 24 mM H+/30 s; pKH, 10.04 +/- 0.87 vs. 8.49 +/- 0.80; and Hill coefficient, 1.67 +/- 0.12 vs. 1.44 +/- 0.10, respectively. Likewise, no significant differences were observed between SHR and WKY cells in either the Km (29 +/- 5 and 32 +/- 8 mM, respectively) or the Vmax (6.0 +/- 1.0 and 5.53 +/- 1.0 mM H+/30 s, respectively) of the sodium activation curve. We conclude that while the ipH of SHR lymphocytes is reduced, the kinetic properties of the Na+/H+ antiporter are virtually identical in SHR and WKY lymphocytes. Consequently, a primary abnormality in the activity of this antiporter is not an inherent feature of lymphocytes from the SHR model of genetic hypertension. We propose that the activity of the Na+/H+ antiporter in SHR cells is apt to be increased as a result of reduction in ipH which dictates a higher set point in its steady-state activity.

Animals↗
PubMed1989

Renal effects of antihypertensive drugs.

Antihypertensive drugs have disparate effects on renal haemodynamics, tubular function, plasma electrolytes, and hormonal responses. Calcium entry blockers and angiotensin-converting enzyme (ACE) inhibitors are unique in that they may increase glomerular filtration rate (GFR) and renal blood flow in patients with hypertension. Both classes of drugs are distinctive in that they prevent salt retention because of their inhibitory effect on tubular sodium reabsorption. In addition to these attributes, which are desirable in terms of lowering systemic blood pressure, these 2 classes of drugs exert important intrarenal effects which may participate in limiting the progression of renal disease. ACE inhibitors have been shown to protect against the development of glomerulosclerosis in various experimental models of renal insufficiency. Importantly, there is emerging evidence from human studies supporting a distinctive beneficial effect of these agents on renal function in patients with hypertension, mild chronic renal insufficiency and diabetes mellitus. Calcium entry blockers have also been shown to exert some beneficial effect in limiting the progression of experimental kidney disease but neither an improvement in glomerular sclerosis nor a decrease in proteinuria have been clearly documented. At present ACE inhibitors appear the most attractive agents in terms of arresting the progression of renal disease. Acute deterioration in renal function may occur following the administration of ACE inhibitors, calcium entry blockers, and beta-blockers. This complication should be considered in every patient on antihypertensive therapy who suffers an unexplained deterioration in renal function. In particular, the sudden deterioration in renal function following initiation of therapy with an ACE inhibitor is a clue to the possible presence of bilateral renal artery stenosis or stenosis of a solitary functioning kidney. Renal damage may also occur in patients with unilateral renal artery stenosis even though total (2-kidney) GFR may not be appreciably reduced. In this setting, a captopril renal scan with hippuran and diethylenetriamine pentaacetic acid (DTPA) provides physiological information regarding the renal blood flow and GFR of each kidney. In patients with unilateral renal artery stenosis the impact of ACE inhibitor therapy on GFR may be discerned by the use of the DTPA scan, which may demonstrate a reduction in GFR in the stenotic kidney that is not apparent by evaluation of total kidney GFR. This suggests that despite adequate control of systemic blood pressure and unchanged plasma creatinine progressive kidney damage in the stenotic kidney ensues.

Animals↗
PubMed1989

Effect of L-arginine on renal tubular bicarbonate reabsorption by the rat kidney.

This study was designed to characterize the effect of L-arginine, a dibasic amino acid, on bicarbonate reabsorption (RHCO3) by the superficial proximal convoluted tubule using the technique of microperfusion in situ and on overall kidney RHCO3 using clearance techniques. Luminal perfusion of proximal tubules with L-arginine (5, 10, and 20 mM) resulted in a concentration-dependent inhibition of RHCO3. Capillary perfusion with L-arginine (10 mM) had no significant effect indicating that this amino acid must gain access into the cell from the luminal side to inhibit RHCO3. The inhibitory effect of L-arginine on RHCO3 was stereospecific since luminal perfusion with D-arginine (10 mM) had no significant effect on RHCO3. The lowest concentration of luminal L-arginine (5 mM) which produced a significant inhibitory effect on RHCO3 (about 13% inhibition) was comparable to that measured in the blood of rats infused with this amino acid (6.4 +/- 0.7 mM). Systemic infusion of L-arginine resulted in metabolic acidosis and only a slight increase in HCO3 excretion. To investigate whether the lack of overt bicarbonaturia was due to the reduced filtered load of HCO3 or to a stimulatory effect of acidemia on distal HCO3 reabsorption, blood bicarbonate was elevated by the infusion of NaHCO3. Under those conditions overall kidney absolute RHCO3, examined as a function of filtered load, was maximal in rats infused with L-arginine, thereby suggesting that when proximal HCO3 transport is inhibited, RHCO3 beyond the end of the proximal convoluted tubule increases in a load-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1988

The use of the urinary anion gap in the diagnosis of hyperchloremic metabolic acidosis.

We evaluated the use of the urinary anion gap (sodium plus potassium minus chloride) in assessing hyperchloremic metabolic acidosis in 38 patients with altered distal urinary acidification and in 8 patients with diarrhea. In seven normal subjects given ammonium chloride for three days, the anion gap was negative (-27 +/- 9.8 mmol per liter) and the urinary pH under 5.3 (4.9 +/- 0.03). In the eight patients with diarrhea the anion gap was also negative (-20 +/- 5.7 mmol per liter), even though the urinary pH was above 5.3 (5.64 +/- 0.14). In contrast, the anion gap was positive in all patients with altered urinary acidification, who were classified as having classic renal tubular acidosis (23 +/- 4.1 mmol per liter, 11 patients), hyperkalemic distal renal tubular acidosis (30 +/- 4.2, 12 patients), or selective aldosterone deficiency (39 +/- 4.2, 15 patients). When the data on all subjects studied were pooled, a negative correlation was found between the urinary ammonium level and the urinary anion gap. We conclude that the use of the urinary anion gap, as a rough index of urinary ammonium, may be helpful in the initial evaluation of hyperchloremic metabolic acidosis. A negative anion gap suggests gastrointestinal loss of bicarbonate, whereas a positive anion gap suggests the presence of altered distal urinary acidification.

Acid-Base Equilibrium↗
PubMed1988

Assessment of collecting tubule hydrogen ion secretion in acute respiratory alkalosis using the urinary pCO2.

The use of the urine-blood (U-B) pCO2 difference as a marker of collecting tubule H+ secretion (CTH+S) faces serious interpretative pitfalls when applied to animals with respiratory acidosis. The present study was aimed to examine the use of this parameter in rats with acute respiratory alkalosis. During infusion of sodium bicarbonate, the U-B pCO2 was only slightly lower in hypocapnic than in eucapnic rats (30 +/- 2.2 and 39 +/- 3.3 mmHg, p less than 0.05) and this difference was no longer significant when this parameter was examined as a function of urine bicarbonate concentration. In contrast, the increment in urine pCO2 elicited by bicarbonate loading (i.e. the delta pCO2) was markedly reduced in hypocapnic as compared to eucapnic rats (22 +/- 3.0 and 38 +/- 4.5 mmHg, respectively, p less than 0.01). The infusion of carbonic anhydrase while the urine was highly alkaline and the blood pCO2 kept constant resulted in a decrement in urine pCO2 which was less in hypocapnic than in eucapnic rats (-23.9 +/- 1.9 vs -33 +/- 2.8 mmHg, p less than 0.02). These findings indicate that pCO2 generation from CTH+S and titration of bicarbonate is reduced in hypocapnic rats. The data are in accord with our proposal that the delta pCO2 is a better index of CTH+S than the U-B pCO2 is the assessment of respiratory acid-base disorders.

Alkalosis, Respiratory↗
PubMed1988

On the mechanism of toluene-induced renal tubular acidosis.

This study was aimed to investigate the pathogenesis of toluene-induced renal tubular acidosis (RTA). In 5 individuals addicted to toluene sniffing we documented the occurrence of hypokalemia and hyperchloremic metabolic acidosis associated with inability to lower urine pH below 5.5 (6.06 +/- 0.24). Overall kidney bicarbonate reabsorption was normal or enhanced, a feature characteristic of the distal form of RTA (DRTA). These findings resemble those found during the administration of amphotericin B, a drug felt to cause DRTA by increasing hydrogen ion (H+) back-diffusion in the collecting tubule. In toluene sniffers, the urine pCO2 measured in a highly alkaline urine was reduced (47 +/- 8.8 mm Hg), suggesting a decrease in the rate of collecting tubule H+ secretion rather than H+ back-diffusion. To investigate these two mechanisms of altered distal acidification more directly we studied the effect of toluene on acidification by the urinary turtle bladder, an epithelial analogue of the mammalian collecting tubule. In this preparation, toluene resulted in a decrease in the rate of H+ secretion measured by either the pH stat technique or the reverse short circuit current. When mucosal pH was progressively lowered to examine H+ secretion against an H+ gradient, toluene-treated bladders displayed a significant decrease in proton conductance but the lowest mucosal pH required to nullify H+ secretion, (MpH) JH = O, was not different from that of control bladders (4.05 +/- 0.29 and 3.90 +/- 0.13, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Renal Tubular↗
PubMed1988

Free cytosolic calcium in renal proximal tubules from the spontaneously hypertensive rat.

Free intracellular calcium was measured in renal proximal tubules obtained from spontaneously hypertensive rats (SHR) and from age-matched Wistar-Kyoto rats (WKY) ingesting a normal diet. Experiments were performed on renal proximal tubule suspensions using fura-2 to monitor cytosolic calcium. In 4-week-old rats, when systolic blood pressure was not significantly different between the two groups, renal proximal tubule cytosolic calcium was similar (143 +/- 28 and 144 +/- 15 nM, respectively). By the age of 5 weeks, cytosolic calcium increased significantly in both SHR and WKY (214 +/- 24 and 262 +/- 34 nM, respectively, p less than 0.05). Calcium, however, was not significantly different between the two groups, even though at this age blood pressure was higher in SHR than in WKY. As compared with values in 4-week-old rats, cytosolic calcium was also found increased in tubules from both SHR and WKY aged 10 to 12 weeks (261 +/- 42 and 279 +/- 30 nM, respectively) and 20 to 24 weeks (263 +/- 42 and 308 +/- 28 nM, respectively). However, no significant differences in cytosolic calcium were found between SHR and WKY even though at these ages systolic blood pressure increased markedly in the SHR. Moreover, regression analysis failed to reveal a correlation between cytosolic calcium and blood pressure when data from either group of rats of all ages studied were pooled. Exposure to ouabain (10(-3) M) to inhibit Na+,K+-adenosine triphosphatase and increase intracellular sodium had no significant effect on cytosolic calcium in tubules from either SHR or WKY (260 +/- 69 and 250 +/- 45 nM, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1988

Patterns of metabolic acidosis in patients with chronic renal failure: impact of hemodialysis.

The type of metabolic acidosis in patients with chronic renal failure was studied prospectively over a three-month period in 32 stable patients on chronic hemodialysis using acetate. All patients had pre-dialysis metabolic acidosis (mean TCO2 = 16.6 +/- 0.4 mEq/l, range 10 to 23 mEq/l). The patterns of metabolic acidosis were defined using the ratio: delta AG/delta TCO2 where delta AG is the increment in plasma anion gap above normal and delta TCO2 the decrement in plasma bicarbonate below normal. The group as a whole showed a mixed hyperchloremic and high anion gap pattern with a mean delta AG/delta TCO2 ratio of 53.3 +/- 7.1%. The individual distribution of patterns ranged from a pure hyperchloremic acidosis (24%) to a pure high anion gap acidosis (30%) with the mixed pattern being the most frequent (46%). An inverse correlation between the TCO2 change (y) during the dialysis procedure and the TCO2 (x) prevailing at the start of dialysis was found by linear regression analysis: y = -0.51x + 11, r = -0.54, p less than 0.01. Thus, before acetate conversion to bicarbonate was fully completed, patients gained bicarbonate during dialysis if TCO2 was less than 21 mEq/l and lost it when the pre-dialysis TCO2 was above this level. On average, the delta AG was reduced to a greater extent than the delta TCO2 so that the delta AG/delta TCO2 ratio fell significantly (from 53 +/- 7.1 to 11 +/- 8.8%, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗
PubMed1987

Prevalence, pathogenesis, and treatment of renal dysfunction associated with chronic lithium therapy.

From the analysis of several studies published from 1979 to 1986 comprising 1,172 patients, we estimated that glomerular filtration rate (GFR) was normal in 85% of unselected patients on chronic lithium therapy. The remaining 15% of patients displayed only mild reduction in GFR, clustering at approximately 60 mL/min. Thus, the data available to date do not support earlier concerns that long-term lithium therapy could eventuate into renal insufficiency. The most prevalent renal effect of lithium is impairment of concentrating ability, which we estimated to be present in at least 54% of 1,105 unselected patients on chronic lithium therapy. This defect translated into overt polyuria in only 19% of unselected cases. A renal lesion confined to the collecting tubule has been described in humans who have taken lithium for short periods of time. This lesion may represent the collecting tubule's response to the intracellular accumulation of lithium, which interferes with cAMP formation and results in an early and probably reversible inhibition of antidiuretic hormone (ADH)-mediated water transport. However, long-term lithium therapy may induce a progressive and partly irreversible defect in concentrating ability. The potential risk for dehydration associated with lithium-induced polyuria, as well as the discomfort inherent to this side effect, deserves evaluation and consideration for therapeutic intervention. Amiloride has additional advantages over conventional treatment of nephrogenic diabetes insipidus using thiazide diuretics. The action of amiloride on ADH-mediated water transport seems specific in as much as it is capable of preventing the uptake of lithium in high resistance epithelia and thereby prevents the inhibitory effect of intracellular lithium on water transport. Unlike thiazides, amiloride has a weak natriuretic effect and is less likely to increase plasma lithium levels by causing volume contraction. In addition, amiloride, by conserving potassium, obviates the need for potassium supplementation that is usually required to prevent hypokalemia when thiazides are used to treat lithium-induced polyuria. Since amiloride may prevent chronic intracellular lithium accumulation in the collecting tubule, future studies should elucidate whether amiloride also has a role in preventing lithium-induced chronic tubulo-interstitial damage.

Acidosis, Renal Tubular↗