enalapril and Potassium-Deficiency

Potassium depletion is associated with a hyperreninemia that may be responsible for some of the renal hemodynamic and functional changes observed in K-deficient states. The present study was designed to evaluate whether interruption of the renin-angiotensin system with enalapril alters the collecting duct changes observed in K depletion. Adrenalectomized male Sprague-Dawley rats were allocated to either a normal (NK) or low-K diet (LK), and they either received enalapril or vehicle for 3 wk. Na:K pump activity (pmol.mm-1.h-1) in microdissected cortical collecting (CCT) and medullary collecting tubules (MCT) was determined at 21 days after group allocations. K depletion had a minimal effect on CCT outer diameter. In contrast, a marked hypertrophy was observed in the MCT diameter (91% increase, P < 0.001) that was significantly attenuated by enalapril treatment (56% increase, P < 0.001 vs. LK). An increase in Na:K pump activity was observed with LK, in the CCT from 497 +/- 47 to 1,089 +/- 83 (P < 0.001) and in the MCT from 489 +/- 36 to 1,396 +/- 45 pmol.mm-1.h-1 (P < 0.01). In K-replete rats, enalapril had no effect on Na:K pump activity in either CCT or MCT. Enalapril administration during LK had no effect on the increase in Na:K pump activity in the CCT (1,023 +/- 75 pmol.mm-1.h-1, P < 0.001), not different from LK alone. In the MCT, however, enalapril reduced the increment in Na:K pump activity induced by LK (1,116 +/- 39 pmol.mm-1.h-1, less than the change with LK alone).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Triphosphatases; Animals; Enalapril; Kidney Cortex; Kidney Medulla; Kidney Tubules, Collecting; Male; Potassium Deficiency; Rats; Rats, Sprague-Dawley; Sodium-Potassium-Exchanging ATPase

The role of the renin-angiotensin system in renal hypokalaemic dysfunction has been investigated by evaluating the effects of the angiotensin (AT)-converting enzyme inhibition by enalapril. Healthy women were studied either in normal potassium balance (N3, n = 6) or moderate potassium depletion (KD3, n = 6). Potassium depletion (KD) was induced by low potassium dietary intake (greater than or equal to 10 mmol per day) and natriuretic treatment associated with replacement of net NaCl and water losses; the cumulative potassium deficit achieved was 214 +/- 54 mmol. The renal function and the urinary excretions of some prostanoids (PGE2, 6-keto-PGF1 alpha, TxB2) were evaluated during hypotonic polyuria (oral water load) and subsequent moderate antidiuresis (lysine-8-vasopressin (LVP) low-dose infusion). Paired studies were performed in absence (control) and presence of enalapril. Basal plasma renin activity (PRA) and urinary aldosterone excretion were determined before the water load of control studies. Renal dysfunction typical of chronic KD occurred in the KD3 group, i.e. increase in PRA, decrease in creatinine clearance, depression of the diuretic response to water load, inhibition of distal fractional chloride reabsorption, and blunted efficacy of LVP in increasing the urinary solute concentration. The urinary prostanoid excretions were reduced. Basal urinary aldosterone excretion was not changed significantly. In KD3 group enalapril decreased mean arterial pressure (MAP), increased the plasma potassium concentration, improved the diuretic response to water load and corrected the impairment of the distal fractional chloride reabsorption. Despite the decrease in MAP enalapril did not affect significantly the creatinine clearance. Neither urinary prostanoid excretions nor the renal response to LVP were affected by the drug. The data suggest that in KD the increased activity of the renin-angiotensin system affected the renal function both through direct effects and through effects dependent on the angiotensin-supported secretions of aldosterone and probably of vasopressin. Finally, by comparing the effects of enalapril and indomethacin in experimental groups with an equivalent degree of KD, evidence is provided in favour of the interaction between renin-angiotensin and prostanoid systems in controlling the glomerular filtration rate and the salt and water handling by renal tubules.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Female; Humans; Indomethacin; Kidney Function Tests; Lypressin; Middle Aged; Potassium Deficiency; Prostaglandins; Radioimmunoassay; Renal Insufficiency; Renin-Angiotensin System

Recently, we have found that transforming growth factor (TGF)-beta 2 and renin are abundantly expressed in the juxtaglomerular apparatus (JGA) of dehydrated mice. Since potassium (K+) depletion also stimulates renin and induces hypertrophy of the JGA, we examined the ability of this maneuver to stimulate TGF-beta isoforms and renin in renovascular tissue and the JGA of young rats. Sprague-Dawley rats (50 +/- 5 g) were fed either a control diet or a potassium-deficient diet (< 0.05% K+) for 7, 16, or 21 days. As a control for TGF-beta and renin stimulation, an additional group of animals was fed a normal diet but was water deprived for three days. Potassium-depleted animals experienced severe growth retardation but kidney weight increased significantly. Potassium depletion induced both TGF-beta 2 and renin immunoreactivity in renal arterioles and the JGA but had no effect on TGF-beta 1 and TGF-beta 3 isoforms. To determine the role of circulating angiotensin II in the stimulation of TGF-beta 2 by potassium depletion, a group of potassium-depleted rats received enalapril (100 mg/liter) in the drinking water. The addition of converting enzyme inhibitor increased both the intensity of TGF-beta 2 and renin staining as well as the number of cells positively stained. Our results demonstrate that K+ depletion induces TGF-beta 2 and renin in renal arterioles and in the JGA. Furthermore, circulating angiotensin II is not responsible for the increase in the local expression of TGF-beta 2. These findings suggest that TGF-beta 2 may be an important mediator of JGA hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Blood Vessels; Enalapril; Immunohistochemistry; Isomerism; Juxtaglomerular Apparatus; Kidney; Male; Potassium Deficiency; Rats; Rats, Sprague-Dawley; Renal Circulation; Renin; Staining and Labeling; Tissue Distribution; Transforming Growth Factor beta

The present studies were designed to test the hypothesis that angiotensin II (ANG II) mediates nonosmotic thirst in animals fed the low-NaCl K-free diet by preventing the increased generation of ANG II using the converting-enzyme inhibitor, enalapril. Animals were fed either a control salt or low-NaCl K-free diet and were treated with or without enalapril. Water intake in rats fed the low-NaCl K-free diet increased more than twofold on day 3 and remained elevated over the 10-day period of study. Treatment with enalapril (40 mg.kg-1.day-1) 1) prevented the striking rise in plasma renin activity in rats fed the low-NaCl K-free diet, 2) led to complete blockade of the pressor response to a 50-ng injection of angiotensin I but not ANG II, 3) did not affect daily water intake in rats consuming the control salt diet, 4) did not reduce basal water intake in rats fed the low-NaCl K-free diet below values measured in control animals, and 5) did not abolish water intake in response to osmotic stimulation. However, enalapril treatment abolished the increase in water intake that occurs in animals fed the low-NaCl K-free diet. In a double crossover study using two groups of rats fed the low-NaCl K-free diet, enalapril prevented increased water intake in rats initially fed the low-NaCl K-free diet and rapidly inhibited increased water intake in rats fed the low-NaCl K-free diet after the high water intake had been established.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Diet; Drinking; Eating; Enalapril; Hydrogen-Ion Concentration; Kidney; Male; Muscles; Potassium; Potassium Deficiency; Rats; Rats, Inbred Strains; Sodium; Sodium Chloride; Thirst