enalapril and Hydronephrosis

The present study investigated the interaction between sodium loading and enalapril on renin synthesis and secretion in hydronephrotic mice. Four different experimental groups (n=10 each) were used: sham-operated animals with normal diet (control group); sodium loading (SL group); enalapril treatment with normal diet (E group), and sodium loading combined with enalapril treatment (SL+E group). The hydronephrotic left kidney was induced by unilateral ureteral ligation in mice in the latter three groups. Plasma renin concentration (PRC) in the aorta, both the left and right renal veins, tissue renin concentration (TRC) and renin mRNA levels in the kidneys were examined under different procedures. In hydronephrotic mice treated with sodium loading, PRC in the left and right renal veins was lower than that in control mice (P<0.05), and TRC and renin mRNA levels in the hydronephrotic kidney were also suppressed (P<0.05). In hydronephrotic mice treated with enalapril, there were significant increases in PRC, TRC and renin mRNA levels in the hydronephrotic and right kidneys compared to the normal control (P<0.01). In hydronephrotic animals treated with sodium loading and enalapril, the increasing response was attenuated, and PRC in the hydronephrotic vein was similar to the level in the aorta. There was an interaction between sodium loading and enalapril on renin-angiotensin system (RAS) in both hydronephrotic and normal kidneys. The mechanism in control of renin synthesis is independent of the macula densa, but the latter is critical in the control of renin secretion.

Topics: Animals; Aorta; Enalapril; Hydronephrosis; Kidney; Mice; Mice, Inbred BALB C; Renin; Renin-Angiotensin System; RNA, Messenger; Sodium

The effects of enalapril and sodium depletion on renin synthesis and secretion were studied in mice with a left hydronephrotic kidney caused by unilateral ureteral ligation (UUL). In the control animals, there was no difference in plasma renin concentration between the right and left renal veins. In mice with left ureteral ligation, the renin concentration in the vein draining the hydronephrotic kidney was similar to or lower than that in the aorta under control conditions and after either stimulation with enalapril or depletion of sodium. Enalapril and sodium restriction increased plasma renin concentration, and this increase was due to secretion from the nonhydronephrotic kidney. The renin concentration per gram of kidney tissue and the mRNA for renin per gram of kidney tissue were similar in both the control and hydronephrotic kidney, and the values rose 3-4-fold in both kidneys after enalapril or sodium depletion. Immunostaining for renin confirmed these findings and indicated that renin per glomerulus was higher in the hydronephrotic kidney. Thus, removal or reduction of angiotensin II activity or depletion of sodium stimulated synthetic activity to a similar extent in the normal and hydronephrotic kidneys; however, secretion from the kidney without a macula densa (hydronephrotic) was not increased. Thus, the signals that control synthesis and secretion are different, and for these stimuli, secretion appears to require an intact macula densa.

Topics: Animals; Enalapril; Hydronephrosis; Male; Mice; Mice, Inbred BALB C; Renin; Renin-Angiotensin System; Sodium

This study defines the nature of the renal protective effects of calcium channel blockers (Ca blockers) and the effects of the Ca blocker, amlodipine, compared to those of the angiotensin-converting enzyme inhibitor (ACEI), enalapril, on the progression of renal injury in 5/6 nephrectomized spontaneously hypertensive rats (SHR) fed a high-salt diet. Furthermore, we studied the effects of various Ca blockers on the glomerular afferent and efferent arterioles using the isolated perfused hydronephrotic kidneys of six-week-old male Sprague-Dawley rats. In the first study, forty 6-week-old male SHRs which underwent 5/6 nephrectomy were equally divided into five groups. One group received no therapy. In two groups, therapy was started at four weeks post-nephrectomy, one with amlodipine and the other with enalapril. In the remaining two groups, amlodipine or enalapril therapy was started at eight weeks postnephrectomy. Amlodipine was more effective than enalapril in reducing proteinuria and glomerulosclerosis in the group that was started on drug therapy eight weeks after surgery. In the second study, at concentrations of 10(-6) to 10(-9) M, nifedipine, nicardipine and amlodipine dilated the afferent, but not the efferent, arteriole preconstricted with angiotensin II. On the other hand, efonidipine and manidipine clearly dilated angiotensin II-induced constriction of both the afferent and efferent arterioles. These results indicated that Ca blockers are effective at reducing renal injury in 5/6 nephrectomized SHR, and that they are more effective than ACEI in advanced stages of renal injury. The observation that only certain Ca blockers can dilate the efferent arteriole suggests that the renal protective effect of Ca blockers is not necessarily dependent on the dilation of the efferent arterioles.

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Calcium Channel Blockers; Enalapril; Hydronephrosis; In Vitro Techniques; Kidney Diseases; Male; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley; Renal Circulation

To determine the effects of hydronephrosis on glomerular number and juxtaglomerular cell synthetic activity and the protective influence of angiotensin converting enzyme inhibition.. A comparison of sham and contralateral kidneys with 8-week ipsilateral ureteral ligated hydronephrotic kidneys in BALB/c mice. Enalapril was administered from 5 weeks in additional sham and hydronephrotic kidney groups.. Renin and prorenin immunohistochemistry was applied to sections of perfusion-fixed kidneys at the light and electron microscope level. Glomerular number was estimated by a physical disector-fractionator stereological method. An enzyme kinetic renin assay was performed in kidney tissue and plasma.. Glomerular number in hydronephrotic kidneys decreased significantly compared with sham and contralateral kidneys. Renin content in hydronephrotic kidneys did not change compared with sham or contralateral kidneys, but the renin content in the glomerulus was significantly greater in hydronephrotic than in contralateral kidneys and similar to in sham kidneys. Contralateral kidneys enlarged significantly and their total renin content decreased significantly compared with hydronephrotic and sham kidneys. Plasma renin was unchanged. Fewer juxtaglomerular cells were labelled for renin and prorenin in contralateral than in hydronephrotic or sham kidneys. Granulopoiesis and exocytotic profiles were markedly greater in hydronephrotic than in contralateral or sham kidneys. Following enalapril, glomerular number was significantly higher in hydronephrotic kidneys and renin content increased proportionally more in contralateral than in hydronephrotic or sham kidneys.. Hydronephrosis for 8 weeks results in atrophy of 50% of glomeruli and exerts an inhibitory influence on contralateral juxtaglomerular cells while augmenting ipsilateral renin production per remaining glomerulus with maintenance of plasma renin. Enalapril preserves glomeruli and reverses the contralateral inhibitory influence, suggesting an angiotensin-related mechanism.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Enalapril; Female; Hydronephrosis; Immunohistochemistry; Juxtaglomerular Apparatus; Kidney; Kidney Glomerulus; Male; Mice; Mice, Inbred BALB C; Microscopy, Electron; Organ Size; Renin

1. Renin synthesis and secretion were investigated in mice with one hydronephrotic kidney. 2. Enalapril and Dup753 stimulated renin synthesis to a similar extent in the hydronephrotic and normal kidney. 3. Hydronephrosis did not prevent an increase in renin mRNA caused by enalapril and Dup753. 4. The results therefore indicate that the macula densa does not appear to be crucial for renin synthesis in the kidney under the inhibition of angiotensin II. 5. Thus angiotensin II plays an important role controlling renin gene expression in both the normal and hydronephrotic kidneys.

Topics: Animals; Antihypertensive Agents; Biphenyl Compounds; Enalapril; Hydronephrosis; Imidazoles; Kidney; Kidney Tubules, Distal; Losartan; Male; Mice; Mice, Inbred BALB C; Renin; RNA, Messenger; Tetrazoles

1. The role of the macula densa in renin synthesis was studied using mice with one hydronephrotic kidney. 2. Renin synthesis was assessed by measurement of renal renin, renal mRNA for renin and plasma renin. 3. Sodium depletion stimulated mRNA and renal renin to a similar extent in the hydronephrotic and contralateral kidney. 4. Enalapril stimulated mRNA concentration in both kidneys but renal renin did not rise in the hydronephrotic kidney. 5. Propranolol did not alter the response to sodium depletion in either kidney. 6. The macula densa is not crucial for the stimulation of renin synthesis following sodium depletion. However, it may regulate renin production after mRNA synthesis, possibly by controlling the conversion of prorenin to renin.

Topics: Animals; Diet, Sodium-Restricted; Enalapril; Hydronephrosis; Kidney; Kidney Tubules; Male; Mice; Mice, Inbred BALB C; Propranolol; Renin; RNA, Messenger

To evaluate the role of angiotensin II (ANG II) in renal vasoconstriction due to ipsilateral CPUO, guinea pigs were subjected to incomplete left ureteral stenosis within the first 48 hr of life, and were given enalapril from the 14th day of life until study at 23 +/- 3 days or 8 weeks of age. Renal blood flow (RBF) was measured using radioactive microspheres, and glomerular filtration rate (GFR) was derived from inulin extraction. The number of perfused glomeruli per kidney was determined following in vivo India ink perfusion. Enalapril treatment resulted in an 83% rise in RBF of the obstructed kidney, from 2.58 +/- 0.26 to 4.73 +/- 0.48 ml/min (P less than 0.001), which was associated with a 26% increase in number of perfused glomeruli (P less than 0.01). Mean GFR of the hydronephrotic kidney increased from 0.13 +/- 0.02 to 0.37 +/- 0.10 ml/min (P less than 0.05). Enalapril had no effect on intraureteral pressure of the obstructed left kidney after 7 to 13 days of administration, and did not affect renal mass or ureteral diameter after 6 weeks of treatment. It is concluded that hemodynamic consequences of CPUO in the neonate may be attenuated by ANG converting enzyme inhibition. The primary effect of enalapril is most likely inhibition of intrarenal ANG II formation.

Topics: Angiotensin II; Animals; Animals, Newborn; Disease Models, Animal; Enalapril; Glomerular Filtration Rate; Guinea Pigs; Hemodynamics; Hydronephrosis; Kidney Glomerulus; Time Factors; Ureteral Obstruction; Vascular Resistance