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(Hypertension. 1995;25:77-81.)
© 1995 American Heart Association, Inc.

Articles

Hypertension After Renal Transplantation

Calcium Channel or Converting Enzyme Blockade?

Margriet R. van der Schaaf; Ronald J. Hené; Marianne Floor; Peter J. Blankestijn; Hein A. Koomans

From the Department of Nephrology, University Hospital Utrecht, and U-Gene Research (M.F.), Utrecht, the Netherlands.

Correspondence to R.J. Hené, MD, Department of Nephrology and Hypertension (Rm F03.226), University Hospital Utrecht, PO Box 85500, 3508 GA Utrecht, the Netherlands.

	Abstract

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Abstract We compared the effects of 4 weeks of calcium channel blockade (amlodipine) or converting enzyme inhibition (lisinopril) on blood pressure and renal hemodynamics in a double-blind crossover trial in a group of 20 hypertensive cyclosporine-treated renal transplant patients. Amlodipine (10 mg) was more effective than the same dose of lisinopril in controlling hypertension (mean 24-hour arterial pressure, 111±9 and 115±9 mm Hg, respectively; P<.05). Blood pressure during both treatments was lower than during placebo (124±12 mm Hg, P<.05). Compared with placebo, amlodipine treatment was associated with a significant increase in glomerular filtration rate (10±20%, P<.05) and effective renal plasma flow (27±20%, P<.01) and a decrease in renal vascular resistance (23±18%, P<.01). Renal hemodynamics did not change during lisinopril. Neither drug had an effect on proteinuria. The data indicate that amlodipine is more effective than lisinopril in controlling hypertension in cyclosporine-treated patients and that treatment with amlodipine but not with lisinopril is accompanied by an increase in glomerular filtration rate and effective renal plasma flow and a decrease in renal vascular resistance. The data suggest that the renin-angiotensin system does not play a main role in determining cyclosporine-associated changes in renal hemodynamics and has a limited role in determining cyclosporine-associated hypertension.

Key Words: vascular resistance • calcium channel blockers • angiotensin-converting enzyme inhibitors • kidney transplantation • antihypertensive therapy

	Introduction

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With the introduction of cyclosporine A (CsA), the graft survival rate after renal transplantation has improved by 10%.¹ However, the use of CsA is associated with a high prevalence of hypertension, affecting up to 70% of the patients. In renal transplant patients on CsA, hypertension is characterized by sodium retention, enhanced sympathetic nervous system activity, renal vasoconstriction, and lower plasma renin levels than in azathioprine-treated patients.² It has been shown that each administration of CsA may induce marked renal vasoconstriction,³ causing a decrease in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). Recent data show that calcium channel blockers can ameliorate the vasoconstrictive effects of CsA,^{2 3 4 5 6 7 8} whereas angiotensin-converting enzyme (ACE) inhibitors do not have such an effect. Theoretically, calcium channel blockers could be superior to ACE inhibitors in reducing hypertension and inducing renal vasodilation in such patients. However, calcium channel blockers predominantly dilate the afferent arteriole and thereby can increase intraglomerular pressure. This might increase proteinuria, which might induce secondary damage to the kidney.

Few studies are available comparing the effects of ACE inhibitors and calcium channel blockers on blood pressure and renal function in CsA-treated renal transplant patients. Comparing these two classes of antihypertensive drugs is of both clinical and pathophysiological interest, especially because in patients on traditional prednisone/azathioprine immunosuppression, hypertension is often characterized by a stimulated renin-angiotensin system generated by the native kidneys.⁹ A recent prospective trial in two parallel groups of such patients on CsA-based immunosuppression demonstrated that hypertension was equally well treated with lisinopril or nifedipine and that the effect on renal function tests was not different.⁷ More accurate comparison could be made in a crossover study, but to our knowledge the available data are limited to a comparison of the effects of 48-hour treatment with either captopril or nifedipine.⁸ The purpose of the present study was to compare the effects on blood pressure and renal function of a calcium channel blocker (amlodipine) and an ACE inhibitor (lisinopril) in a double-blind crossover design in patients with renal transplantation and CsA-induced hypertension.

	Methods

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Patients
Inclusion criteria for the study were the following: renal transplant patients with one or two native kidneys still present, on CsA and prednisone therapy, stable renal function with a plasma creatinine level less than 250 µmol/L for the 6 months before the study, no graft site bruit, and a diastolic blood pressure between 95 and 125 mm Hg 2 weeks or more after discontinuation of antihypertensive and diuretic treatment. We selected 20 patients (12 men) from our transplant program who fulfilled these criteria. Their age (mean±SD) was 42.8±12.8 years and they were 3.3±2.1 (range, 1 to 8) years since transplantation. Eighteen patients were Caucasian and 2 Asians. Two grafts were derived from living related donors and 18 from cadaveric donors. The primary renal diagnoses were glomerulonephritis (n=11), congenital abnormalities (n=3), nephrosclerosis (n=2), Alport's syndrome (n=1), medullary cystic disease (n=1), adult polycystic disease (n=1), and unknown (n=1). Nine patients were hypertensive before transplantation. The dosage of prednisone was 7.5 to 10 mg/d and of CsA 4.4±1.4 mg/kg per day. Target trough level of CsA (Sandimmune) was 80 to 150 ng/mL.

Study Protocol
The study was performed in a double-blind crossover design. After having tapered off their hypertension medication at least 2 weeks before, patients started the study using placebo tablets for 2 weeks (single-blind). After completion of the placebo phase, patients were randomized into two groups, one starting with amlodipine 5 mg once daily and the other with lisinopril 5 mg once daily. When office blood pressure exceeded 150/95 mm Hg after 2 weeks of treatment, the dose was increased to 10 mg of the study drug. After 4 weeks of active drug treatment and a second washout period of 4 weeks, during which the patients were using placebo tablets, the patients were switched to the other drug and followed the same protocol.

Patients were seen at weeks 0, 1, and 2 (first placebo phase); weeks 4 and 6 (first part of the crossover trial); week 10 (after second placebo period); and weeks 12 and 14 (second part of the crossover trial). During these visits, sitting blood pressure was measured with a standard mercury sphygmomanometer after patients had rested at least 5 minutes. Renal clearance studies were performed at weeks 2 (end of the first placebo phase), 6, and 14 (after the two periods of active treatment). The day before renal function measurements were done, 24-hour blood pressure was measured noninvasively. At the end of the first placebo phase (week 2), blood was taken for plasma renin activity determination after the patients had been in a recumbent position for at least 90 minutes. The protocol was approved by the Medical Ethics Committee of the University Hospital Utrecht, and written informed consent was obtained from all subjects.

Laboratory Methods
GFR and ERPF were estimated as described elsewhere.¹⁰ In brief, the left and right cubital veins were cannulated, one for blood sampling and one for a sustained infusion of inulin (10%) and para-aminohippuric acid (PAH 2.5%), preceded by a priming dose. All studies were performed in the morning after the patients had taken their drugs. The clearance study was started after a 90-minute equilibration period. This study consisted of two 60-minute periods during which urine was collected by spontaneous voiding. Midpoint plasma samples were taken for inulin and PAH determination. To produce sufficient urine, an oral water load of 25 mL/kg body wt was provided before the study and additional water matching diuresis during the study. GFR and ERPF were calculated according to the standard clearance formula using inulin hippurate. Renal vascular resistance (RVR) was calculated using the following formula: MAPx(1-hematocrit)/ERPF, where MAP is mean arterial pressure. Throughout the experiment, blood pressure was measured by an automated cuff inflation device at 10-minute intervals. MAP was calculated as diastolic blood pressure+ pulse pressure.

Routine blood tests were done using standard laboratory methods. Whole-blood CsA levels were measured by high-performance liquid chromatography, and plasma renin activity was measured by radioimmunoassay.¹¹ Inulin was measured photometrically with indoleacetic acid after hydrolyzation to fructose¹² and PAH photometrically by a chromogenic aldehyde reaction.¹³

Twenty-four–hour blood pressure was measured noninvasively with a Spacelabs 90207 device. During the day (7 AM to 11 PM), blood pressure was measured every 15 minutes and during the night (11 PM to 7 AM) every 60 minutes. Mean hourly blood pressure and the mean of the 24 hourly means were calculated.

Statistics
Data are presented as mean±SD. Statistical analysis was performed by one-way ANOVA for repeated measurements. If variation ratios reached statistical significance (P<.05), the differences between the means were analyzed by t test for paired observations with Bonferroni's protection and the least significant difference test. Correlation was tested by the Spearman rank correlation test.

	Results

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During both drug regimens, 6 patients were titrated to the lower dose of 5 mg and 14 patients to the higher dose of 10 mg so that the average dosage was 8.5 mg/d of either drug. Office blood pressure after the first washout period did not differ from that measured during the intermediate placebo period (175/108 and 169/106 mm Hg, respectively). Systolic and diastolic pressures and MAP determined either manually or by 24-hour measurement decreased in all but 1 patient during treatment with amlodipine as well as with lisinopril. The average 24-hour MAP was lower during both drug treatments compared with placebo. However, blood pressure was significantly lower (P<.05) during amlodipine than lisinopril (Table 1 and Fig 1). Mean baseline plasma renin activity was 426±58 (range, 150 to 800) fmol/L per second. There was no relation between the decrease in blood pressure and pretreatment plasma renin activity.

View this table: [in this window] [in a new window]   Table 1. Blood Pressure, Serum Creatinine, Cyclosporine A Trough Levels, Urinary Sodium, and Body Weight During Placebo and Antihypertensive Treatment

View larger version (13K): [in this window] [in a new window]   Figure 1. Line graph shows hourly averages of mean arterial blood pressure. indicates placebo; , amlodipine; and , lisinopril.

GFR and ERPF were higher (10±20% and 27±20%, respectively) and serum creatinine was lower during amlodipine treatment compared with placebo (Fig 2), whereas renal function parameters during lisinopril were not significantly different from placebo (Table 2). Filtration fraction did not change significantly with either drug. RVR decreased by 23±18% during amlodipine compared with placebo, whereas no significant change was found during lisinopril. There was no relation between baseline plasma renin activity and change in RVR.

View larger version (14K): [in this window] [in a new window]   Figure 2. Bar graph shows change in renal hemodynamics relative to placebo during treatment with lisinopril (black bars) and amlodipine (hatched bars). GFR indicates glomerular filtration rate; ERPF, effective renal plasma flow; and RVR, renal vascular resistance. *P<.05, **P<.01 vs placebo.

View this table: [in this window] [in a new window]   Table 2. Results of Renal Function Studies

Proteinuria (>0.5 g/d) was apparent in 13 patients. Mean proteinuria in those patients during placebo, amlodipine, and lisinopril amounted to 0.95±0.51, 1.0±0.67, and 0.75±0.35 g/d, respectively (P=NS). During amlodipine treatment, slightly higher CsA trough levels were observed (Table 1).

	Discussion

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In this study we demonstrate that 24-hour blood pressure in CsA-treated renal transplant patients after 4 weeks of treatment with amlodipine or lisinopril was lower than during placebo. However, the antihypertensive effect of amlodipine was somewhat more pronounced than that of lisinopril (Fig 1). Furthermore, amlodipine treatment resulted in an increase in GFR and ERPF and a decrease in RVR, whereas these variables remained unchanged during lisinopril treatment (Fig 2).

Possible mechanisms of hypertension in CsA-treated renal transplant patients include enhanced sympathetic nervous system activity, renin-angiotensin system activation, change in the balance of vasodilator and vasoconstrictor prostaglandins, intrinsic vasoconstrictor activity of CsA, and increased endothelin production.² The hypertension is generally characterized by sodium and water retention and is relatively unresponsive to ACE inhibition.¹⁴ Furthermore, CsA has been shown to be a potent renal vasoconstrictor agent, affecting the afferent arteriole.² Recently, it has been established that each single dose of CsA produces a marked fall in GFR and ERPF and rise in RVR in renal transplant patients and that the calcium channel blocker lacidipine abolishes these effects of CsA.³ This renal vasoconstrictive action may be explained by an increased endothelin production.^{15 16} Animal experiments have shown that endothelin-induced vasoconstriction depends on the activation of L-type calcium channels, which are the main target for calcium channel blocking agents.^{17 18 19} This may explain why calcium channel blockers have a clear hypotensive as well as renal vasorelaxant effect in patients treated with CsA. Additionally, calcium channel blockers have been shown to antagonize the effects of several of the putative CsA-stimulated hormonal factors, such as angiotensin II and norepinephrine.²⁰ Finally, it is of interest that favorable effects of 3 fatty acids on systemic vascular resistance and RVR have been reported in CsA-treated renal and heart transplant patients, comparable to the effects of calcium channel blockers.^{21 22} As this "fish oil" presumably acts by changing the prostaglandin profile by decreasing the production of vasoconstrictive thromboxane A₂ and increasing that of the vasodilator prostacyclin I₃,²³ this adds evidence to the hypothesis that prostaglandins may play a role in CsA-induced vasoconstriction. Calcium channel blockers may also antagonize the effects of thromboxane A₂.²⁴

We found a significant antihypertensive effect of lisinopril, which was somewhat less pronounced than that of amlodipine at least in the doses used in the study. Studies in subjects with moderate renal insufficiency have shown that 5 to 10 mg lisinopril once daily is sufficient to block 80% of the converting enzyme activity for 24 hours.²⁵ Therefore, it is unlikely that the observed difference in antihypertensive effect is due to an insufficient dose of lisinopril. This observation suggests that the vasoactive systems modulated by ACE inhibition, that is, the renin-angiotensin and kinin systems, are to some extent involved in determining hypertension associated with CsA treatment. However, the data also suggest that these systems do not contribute in a major way to determining CsA-mediated changes in renal hemodynamics, because no effect of lisinopril treatment on renal parameters was found. Apparently, other mechanisms, on which amlodipine has greater effects, are of overriding importance. Taken together, our results support the view that whereas hypertension in azathioprine-treated patients is mainly caused by increased activity of the renin-angiotensin system generated by the native kidneys⁹ and responds well to ACE inhibition, also causing renal vasodilatation, in CsA-treated patients the pathophysiology of the systemic and renal hemodynamics is more complex, involving other mechanisms besides renin production by the native kidneys.

In the 13 patients with proteinuria exceeding 0.5 g/d in the placebo phase, we evaluated the effects of drug treatment on protein excretion. We found no significant effect of either drug on proteinuria. The amlodipine-associated increase in GFR was probably caused by afferent renal vasodilatation, which could have resulted in an increase in intraglomerular pressure and subsequently an increase in proteinuria. Proteinuria is also determined by the glomerular capillary ultrafiltration coefficient (K_f). It has been shown in micropuncture experiments that short-term administration of CsA decreases K_f,²⁶ which may form the basis of the potent antiproteinuric properties of CsA.² It has also been demonstrated in studies of cultured mesangial cells that calcium channel blockade does not ameliorate the CsA-induced decrease in K_f.^{27 28} As all data on K_f are derived from animal experiments only, extrapolation to the human situation is speculative. However, the findings would provide a theoretical basis to explain the absence of an increase of proteinuria during amlodipine administration. This is also in line with our finding that filtration fraction did not change significantly during amlodipine treatment. Other researchers have also found no increase in proteinuria in CsA-treated renal transplant patients with a calcium channel blocker.^{4 7}

The pathophysiology of CsA nephrotoxicity is complex, including tubular toxicity, renal vasoconstriction, morphological abnormalities in the renal vasculature, and changes in glomerular permeability.² Whether calcium channel blockade, apparently efficient in preventing the renal vasoconstriction caused by CsA, is helpful in preventing long-term CsA nephrotoxicity remains to be established. Preliminary data by Morales et al²⁹ indicate that this may be the case. It is particularly reassuring that the calcium channel blockers used in the present study did not increase proteinuria because glomerular filtration of proteins and other macromolecules may be detrimental to kidney function.³⁰ However, the follow-up in our study was limited to 4 weeks, so we cannot exclude long-term effects on proteinuria.

Because CsA is subject to extensive hepatic metabolism by the cytochrome P-450 mono-oxygenase system,³¹ it is clear that drugs that inhibit this system, such as calcium channel blockers, interfere with CsA elimination. This has been shown for verapamil, diltiazem, and nicardipine, which cause up to a threefold increase in CsA trough level,^{32 33} whereas it has been reported that nifedipine, isradipine, and nitrendipine do not affect CsA metabolism. We found slightly elevated CsA trough levels (23% higher) during amlodipine (Table 1), suggesting that amlodipine also interferes to some extent with CsA metabolism. These effects of amlodipine underscore the results on renal hemodynamics, as RVR decreased despite the higher CsA blood levels.

In conclusion, we showed that amlodipine is more effective than lisinopril in controlling hypertension in CsA-treated renal transplant patients and that treatment with amlodipine but not with lisinopril is associated with a consistent increase in GFR and ERPF and a decrease in RVR. The data suggest that besides the renin-angiotensin system, other pressure systems are involved in the pathogenesis of CsA-induced changes in renal and systemic hemodynamics. Whether this effect of calcium channel blockers on renal hemodynamics is helpful in minimizing the development of irreversible CsA nephrotoxicity remains to be established.

Received August 8, 1994; first decision September 8, 1994; accepted October 3, 1994.

	References

Top Abstract Introduction Methods Results Discussion References

 
1. Reeve CE. A randomized clinical trial of cyclosporine in cadaveric renal transplantation. N Engl J Med. 1983;309:809-815. [Abstract]

2. McNally PG, Feehally J. Pathophysiology of cyclosporin A nephrotoxicity: experimental and clinical observations. Nephrol Dial Transplant. 1992;7:791-804. [Free Full Text]

3. Ruggenetti P, Perico N, Mosconi L, Gaspari F, Benigni A, Amuchastegui CS, Bruzzi I, Remuzzi G. Calcium channel blockers protect transplant patients from cyclosporine-induced daily renal hypoperfusion. Kidney Int. 1993;43:706-711. [Medline] [Order article via Infotrieve]

4. Berg KJ, Holdaas H, Endresen L, Fauchald P, Hartmann A, Pran T, Solbu D. Effects of isradipine on renal function in cyclosporine-treated renal transplant patients. Nephrol Dial Transplant. 1991;6:725-730.

5. Abu-Romeh SH, El-Khatib D, Rashid A, Patel M, Osman N, Fayyad M, Scheikhoni A, Higazi AS. Comparative effects of enalapril and nifedipine on renal hemodynamics in hypertensive renal allograft recipients. Clin Nephrol. 1992;37:183-188. [Medline] [Order article via Infotrieve]

6. Textor SC, Schwartz L, Wilson DJ, Wiesner R, Romero JC, Augustine J, Kos P, Hay E, Gores G, Dickson ER, et al. Systemic and renal effects of nifedipine in cyclosporine-associated hypertension. Hypertension. 1994;23(suppl I):I-220-I-224.

7. Mourad G, Ribstein J, Mimran A. Converting-enzyme inhibitor versus calcium antagonist in cyclosporine-treated renal transplants. Kidney Int. 1993;43:419-425. [Medline] [Order article via Infotrieve]

8. Curtis JJ, Laskow DA, Jones PA, Julian BA, Gaston RS, Luke RG. Captopril-induced fall in glomerular filtration rate in cyclosporine-treated hypertensive patients. J Am Soc Nephrol. 1993;3:1570-1574. [Abstract]

9. Curtis JJ, Luke RG, Diethelm AG, Whelchel JD, Jones P. Benefits of removal of native kidneys in hypertension after renal transplantation. Lancet. 1985;2:739-742. [Medline] [Order article via Infotrieve]

10. Boer WH, Koomans HA, Dorhout Mees EJ. Lithium clearance during the paradoxical natriuresis of hypotonic expansion in man. Kidney Int. 1987;32:376-381. [Medline] [Order article via Infotrieve]

11. Boer P, Hené RJ, Koomans HA, Nieuwenhuis MG, Geyskes GG, Dorhout Mees EJ. Blood and extracellular fluid volume in patients with Bartter's syndrome. Arch Intern Med. 1983;143:1902-1905. [Abstract/Free Full Text]

12. Heyrowski A. A new method for determination of inulin in plasma and urine. Clin Chim Acta. 1956;1:470-474. [Medline] [Order article via Infotrieve]

13. Waugh WH, Beall PT. Simplified measurement of p-amino-hippurate and other arylamines in plasma and urine. Kidney Int. 1974;5:429-436. [Medline] [Order article via Infotrieve]

14. Curtis JJ. Hypertension after renal transplantation: cyclosporine increases the diagnostic and therapeutic considerations. Am J Kidney Dis. 1989;13(suppl 1):28-32.

15. Kon V, Sugiura M, Inagami T, Harvie BR, Ichikawa I, Hoover R. Role of endothelin in cyclosporine-induced glomerular dysfunction. Kidney Int. 1990;37:1487-1491. [Medline] [Order article via Infotrieve]

16. Bunchman TE, Brookshire CA. Cyclosporine-induced synthesis of endothelin by cultured human endothelial cells. J Clin Invest. 1991;88:310-314.

17. Edwards RM, Trizna W, Ohlstein EH. Renal microvascular effects of endothelin. Am J Physiol. 1990;259:F217-F221. [Abstract/Free Full Text]

18. Epstein M. Calcium antagonists and the kidney. Am J Hypertens. 1993;6:251S-259S. [Medline] [Order article via Infotrieve]

19. Bloom ITM, Bentley FR, Garrison RN. Acute cyclosporine-induced renal vasoconstriction is mediated by endothelin-1. Surgery. 1993;114:480-488. [Medline] [Order article via Infotrieve]

20. Weir MR. Calcium channel blockers in organ transplantation: important new therapeutic modalities. J Am Soc Nephrol. 1990;1:S28-S38.

21. Homan van der Heide JJ, Bilo HJG, Tegzess AM, Donker AJM. The effects of dietary supplementation with fish oil on renal function in cyclosporine-treated renal transplant patients. Transplantation. 1990;49:523-527. [Medline] [Order article via Infotrieve]

22. Ventura HO, Milani RV, Lavie CJ, Smart FW, Stapleton DD, Toups TS, Price HL. Cyclosporine-induced hypertension: efficacy of -3 fatty acids in patients after cardiac transplantation. Circulation. 1993;88(part 2):281-285.

23. Leaf A, Weber PC. Cardiovascular effects of n-3 fatty acids. N Engl J Med. 1988;318:549-557. [Medline] [Order article via Infotrieve]

24. Loutzenhiser R, Epstein M, Horton C, Sonke JP. Reversal of renal and smooth muscle actions of the thromboxane mimetic U-44069 by diltiazem. Am J Physiol. 1986;19:F619-F626.

25. van Schaik BAM, Geyskes GG, Boer P. Lisinopril in hypertensive patients with and without renal failure. Eur J Clin Pharmacol. 1987;32:11-16. [Medline] [Order article via Infotrieve]

26. McNally PG, Walls J, Feehally J. The effect of nifedipine on renal function in normotensive cyclosporin-A-treated renal allograft recipients. Nephrol Dial Transplant. 1990;5:962-968.

27. Barros EJG, Boim MA, Ajzen H, Ramos OL, Schor N. Glomerular hemodynamics and hormonal participation on cyclosporin nephrotoxicity. Kidney Int. 1987;32:19-25. [Medline] [Order article via Infotrieve]

28. Rodríguez-Puyol D, Lamas S, Olivera A, López-Farré, Ortega G, Hernando L, López-Novoa JM. Actions of cyclosporin A on cultured rat mesangial cells. Kidney Int. 1989;35:632-637. [Medline] [Order article via Infotrieve]

29. Morales JM, Rodriguez-Paternina E, Anders A, Hernandez E, Ruilope LM, Rodicio JL. Long-term protective effect of calcium antagonist on renal function in hypertensive renal transplant patients on cyclosporine therapy: a five-year prospective randomized study. In: Proceedings of the Third International Congress on Cyclosporine; March 25-31, 1994; Seville, Spain. Abstract 154.

30. Remuzzi G, Bertani T. Is glomerulosclerosis a consequence of altered glomerular permeability to macromolecules? Kidney Int. 1981;19:384-394.

31. Maurer G, Lemaire M. Biotransformation and distribution in blood of cyclosporine and its metabolites. Transplant Proc. 1986;18(suppl 5):25-34.

32. Lindholm A, Henricsson S. Verapamil inhibits cyclosporin metabolism. Lancet. 1987;1:1262-1263.

33. Çopur MS, Tasdemir I, Turgan Ç, Yasavul Ü, Çaglar . Effects of nitrendipine on blood pressure and cyclosporin A level in patients with posttransplant hypertension. Nephron. 1989;52:227-230.[Medline] [Order article via Infotrieve]

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