(Hypertension. 1997;29:70.)
© 1997 American Heart Association, Inc.
Research Articles (Issue 1, Part 1) |
Urinary Endothelin-1 Excretion Is Enhanced by Low-Dose Infusion of Brain Natriuretic Peptide in Normal Humans
the Department of Clinical Pathophysiology, Endocrine Unit (M.L. De F., C.P., M.M.); Institute of Internal Medicine, Cardiovascular Unit (G. La V., C.L., C.T.-G.); and Institute of Obstetrics and Gynecology Clinic (A.B.), University of Florence (Italy).
Correspondence to Massimo Mannelli, MD, Department of Clinical Pathophysiology, Endocrine Unit, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy. E-mail m.mannelli@mednuc2.dfc.unifi.it
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Abstract |
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To evaluate the functional relationship between cardiac natriuretic peptides and endothelin-1 within the human kidney, we studied the effects exerted by infusion of brain natriuretic peptide on urinary endothelin-1 excretion. We studied twice in a single-blind manner five normal volunteers who received a constant infusion of 5% dextrose (250 mL/h) or human brain natriuretic peptide-32 at a dose of 4 pmol/kg per minute. Blood samples were drawn at intervals for measurement of hematocrit and concentrations of creatinine, electrolytes, brain natriuretic peptide, and endothelin-1. Urine was collected at intervals for measurement of flow rate and concentrations of creatinine, sodium, cGMP, and endothelin-1. Blood pressure and heart rate were measured every 15 minutes. Placebo administration did not change blood pressure, heart rate, or any of the other parameters measured in plasma and urine. As expected, brain natriuretic peptide infusion caused significant increases in its own plasma levels (basal versus peak levels [mean±SD], 1.45±0.20 versus 50.5±6.0 pmol/L, P<.01), in urinary cGMP (0.75±0.16 versus 1.92±0.81 fmol/min, P<.05), and in urinary sodium excretion (140.0±38.7 versus 624.2±181.6 µmol/min, P<.01). In addition, it caused an increase in urinary endothelin-1 excretion (4.32±2.11 versus 19.67±9.52 fmol/min, P<.05), without modifying plasma endothelin-1, blood pressure, heart rate, creatinine clearance, and urinary flow rate. Our data indicate that brain natriuretic peptide, at plasma levels comparable to those observed in patients with heart failure, causes a significant increase in urinary but not plasma endothelin-1, thus demonstrating a functional link between cardiac natriuretic peptides and renal release of endothelin-1.
Key Words: brain natriuretic peptide • endothelin • kidney • natriuresis
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Introduction |
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The kidney plays a pivotal role in body fluid and cardiovascular homeostasis through the control of water and sodium excretion. Diuresis and natriuresis are very complex functions regulated by many neuronal and hormonal factors. ET-1, a 21–amino acid vasoconstrictor peptide isolated from the culture medium of porcine aortic endothelial cells,1 is one of the factors involved in kidney function. At the same time, the kidney is a source of and target for ET-1. Prepro-ET-1 mRNA has been demonstrated in human kidney by either in situ hybridization techniques or Northern blot analysis.2 ET-1 gene expression and synthesis have been demonstrated in cultured human inner medullary collecting duct cells,3 and in urine, ET-1 is present at concentrations higher than in blood.4 Moreover, ET-1–like immunoreactivity has been detected in both human renal cortex and medulla homogenates,5 and ET-1 binding sites have been demonstrated in human kidney by autoradiographic studies.6 7
ET-1 may affect renal function acting at different levels. When infused into the general circulation, it causes an increase in renal vascular resistance and decrease in renal plasma flow and glomerular filtration rate.8 9 The role of ET-1 in renal sodium excretion is still unclear. While some,8 10 11 but not all,9 12 studies suggest an antinatriuretic effect of systemically infused ET-1, in the isolated perfused kidney, ET-1 causes a natriuretic effect that is independent of changes in filtered load.13 14 15
ET-1 is functionally linked, in a complex and still unclear manner, to other factors involved in kidney function, particularly the cardiac natriuretic peptides ANP and BNP. In fact, ANP infusion reverses ET-1 effects on renal vascular resistance and renal plasma flow,10 and ANP inhibits ET-1 secretion by endothelial cells.16 Conversely, ET-1 infusion elevates circulating levels of ANP.8 11 On the other hand, ET-1 also possesses synergistic actions with ANP in the kidney; in fact, similarly to ANP, ET-1 can induce natriuresis9 13 14 15 and suppresses renin secretion.17 18 19
In an attempt to further investigate the role played by renal ET-1 and the functional relationship, at the kidney level, between cardiac natriuretic peptides and ET-1 in humans, we studied the effects exerted by BNP on kidney function and ET-1 excretion.
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Methods |
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Experimental Protocol
Five healthy volunteers (two men and three women; age range, 28 to 38 years) gave their informed consent to participate in the study, which was approved by the local Ethics Committee. Subjects had no history of cardiovascular, renal, hepatic, or metabolic disease, and none was taking medication. All the volunteers had normal BP levels, plasma and urinary electrolytes, blood cell counts, electrophoresis of serum proteins, and renal function. The subjects were on a free diet. On the day of the study, they fasted from midnight and at 8 AM were referred to the study room. An antecubital vein in each arm was cannulated for infusion of substances and blood sampling. The cuff of an automated apparatus (Dinamap, Critikon), validated against a standard sphygmomanometer before each experiment, was placed on the nondominant arm for BP and heart rate recordings. Thereafter, an infusion of 5% dextrose (250 mL/h) was started and continued throughout the study to maintain adequate urine flow rates, thereby increasing the accuracy of urine collections. After 1 hour of equilibration, urine was obtained by spontaneous voiding and discarded. Immediately afterwards, six consecutive 45-minute clearance periods were performed before (first and second periods), during (third and fourth periods), and at the end of (fifth and sixth periods) administration of synthetic hBNP-32 (Clinalfa, 4 pmol/kg per minute) or placebo (Fig 1). BNP solution was prepared by dissolving the calculated amount of synthetic hBNP in 10 mL haemaccel (Behring) and was added to the 5% glucose solution. Haemaccel was used as a peptide carrier because it minimizes BNP losses caused by absorption onto the walls of the infusion set.20 Placebo consisted of the same vehicle (haemaccel, 10 mL) without BNP. Blood samples were obtained in the middle of each clearance period for determination of hematocrit and concentrations of creatinine, electrolytes, BNP, and ET-1. Urine was collected by spontaneous voiding at the end of each clearance period for measurement of urine flow and urinary excretions of creatinine, sodium, cGMP, and ET-1. BP and heart rate were measured every 15 minutes throughout the study. All subjects remained supine except when voiding. The above protocol was repeated after 4 days, crossing over the treatments.
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Plasma and Urine Measurements
Blood samples (3 mL) for creatinine, hematocrit, and electrolytes were collected in silicone-coated tubes and assayed within 2 hours with an automatic Multianalyzer instrument. Blood samples (7 mL) for hBNP-32 and ET-1 determination were collected in ice-chilled tubes containing EDTA and aprotinin (Trasylol, Bayer; 3500 kallikrein inhibiting units). Samples were centrifuged within 30 minutes at 4°C and 1500g, and plasma was stored at -80°C until further processing. hBNP-32 was extracted from 2 mL plasma with Sep-Pak C18 cartridges (Waters Associates) and measured by radioimmunoassay (Peninsula Laboratories), as reported elsewhere.21
ET-1 was extracted from 5 mL plasma or 2.5 mL urine with Sep-Pak C18 cartridges previously activated with acetonitrile/trifluoroacetic acid/water (60:0.1:39.9, vol/vol/vol) and washed with water/trifluoroacetic acid (99.9:0.1, vol/vol). Elution fractions were lyophilized, and the dry residue was stored at -80°C until assayed. The overall extraction recovery, as assessed by 125I–ET-1, averaged 85%. ET-1 immunoreactivity in extracted samples was determined by a previously described radioimmunoassay,22 with minor modifications. Briefly, samples were resuspended in 250 µL radioimmunoassay buffer (phosphate-buffered saline, pH 7.4, containing 0.1% bovine serum albumin, 0.1% Triton X-100, 1 mmol/L EDTA, 155 mmol/L NaCl, and 0.01% NaN3). Both ET-1 standard (Novabiochem) and test samples (100 µL) were mixed with 100 µL antiserum (Peninsula) diluted with radioimmunoassay buffer (final dilution, 1:72 000). The reaction mixture was incubated for 24 hours at 4°C, and then 12 000 cpm 125I–ET-1 (Amersham International) was added and the incubation was continued for an additional 24 hours at 4°C. Separation of free from antibody-bound 125I–ET-1 was achieved by addition of a mixture containing a second antibody (goat anti-rabbit, 1:200), normal rabbit serum (1:2000), and polyethylene glycol 6000 (7.5%) for 30 minutes at 22°C. After 30 minutes, 1 mL radioimmunoassay buffer was added to stop the reaction, and immunoprecipitates were centrifuged at 4000 rpm for 30 minutes at 4°C. Supernatants were removed, and pellet radioactivity was detected with a gamma counter. The minimum detectable concentration was 0.4 pg per tube; nonspecific binding did not exceed 2% of total radioactivity.
Urinary cGMP was measured with a commercial kit (NEN-DuPont). Results of urine measurements were corrected for the corresponding urine flow rates and expressed as the urinary excretion rates of sodium, cGMP, and ET-1.
Statistical Analysis
Data are reported as mean±SD. Comparison between the set of data obtained during placebo and BNP infusions was performed by repeated measures ANOVA, followed by Student's t test for paired data with the Bonferroni correction when appropriate to adjust probability values for multiple comparisons. A value of P<.05 was considered to be statistically significant.
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Results |
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Intravenous administration of 5% glucose solution (250 mL/h) throughout the study did not lead to significant changes in intravascular volume, as assessed by plasma hematocrit determination during placebo administration (change in percent plasma volume versus baseline, -1.22±2.0 and +0.32±3.24 after 2 and 4 hours, respectively; P=NS). No significant differences were found in heart rate and BP (Fig 2) during either placebo or BNP infusion. Placebo administration did not cause any significant change in plasma creatinine, plasma sodium, plasma proteins, creatinine clearance, or urinary flow rate (Table); plasma BNP or urinary cGMP and sodium (Fig 3); or plasma and urinary ET-1 (Fig 4).
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P<.001.
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hBNP administration did not cause significant changes in plasma creatinine, plasma proteins, plasma sodium (Table), and plasma ET-1 (Fig 4, top), although a tendency toward a decrease of values with time was observed. Similarly, hBNP administration did not cause significant changes in creatinine clearance and urine flow rate (Table). As expected, hBNP infusion caused a significant increase in plasma BNP (Fig 3, top) (up to 50.5±6.0 pmol/L, P<.001 versus basal and placebo values), urinary cGMP (Fig 3, middle) (up to 1.92±0.81 fmol/L, P<.05 versus basal and placebo values), and urinary sodium excretion (Fig 3, bottom) (up to 624.2±181 µmol/min, P<.01 versus basal and placebo values). In addition, hBNP infusion was able to increase urinary ET-1 (Fig 4, bottom) (up to 19.7±9.5 fmol/min, P<.05 versus basal and placebo values). Urinary ET-1 levels started increasing significantly 45 minutes from the beginning of the infusion and were still elevated 90 minutes after the end of treatment.
Urinary excretion of ET-1 as well as the other parameters measured in urine did not differ when expressed as units per milligram creatinine.
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Discussion |
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In vitro and in vivo studies agree overall that the kidney is able to synthesize ET-1 and release it into urine23 and that ET-1 measured in urine is of renal origin.24 In fact, it is now generally accepted that plasma and urinary ET-1 represent two different endothelin-generating systems,25 and our results confirm this hypothesis, as BNP caused a significant increase in urinary ET-1 without affecting plasma ET-1 levels.
It is still unknown which part of the kidney contributes mainly to urinary ET-1 excretion, and to what extent. In fact, within the kidney, ET-1 has been shown to be synthesized at the glomerular, endothelial, and epithelial cell levels.2 24 26 As in vitro studies clearly demonstrate that the greatest concentrations of ET-1, as measured by radioimmunoassay27 or immunoperoxidase staining,26 are contained in the renal medulla, this latter very likely is the major determinant of urinary ET-1 levels. Within the medulla, as demonstrated by in situ hybridization, the vasa recta bundles and capillaries, together with the inner medullary collecting tube cells,2 seem to contribute to ET-1 synthesis to the greatest extent. Whether urinary ET-1 derives mainly from the endothelial or tubular components of the renal medulla is still undetermined.
Whatever the source, urinary ET-1 excretion varies in different physiological and pathological conditions. In humans, ET-1 excretion varies during acute volume expansion25 and after postural changes.28 Infusion of a 5% glucose solution at large doses (20 mL/kg per hour) causes a decrease in urinary ET-1 excretion, whereas upright posture causes an increase. The physiological role exerted by renal ET-1 in cardiovascular and renal responses to these stimuli is still unclear.
In our subjects, placebo administration of 5% glucose at 250 mL/h did not cause any change in BP or heart rate or any of the plasma and urinary parameters. These findings are in agreement with those obtained by Neri Serneri et al25 when infusing 5% glucose at low doses. These authors observed a significant decrease (-99%) in human ET-1 urinary excretion only when infusing large doses of 5% dextrose. As such volume expansion caused a significant increase in plasma ANP and as ANP is able to reduce basal and stimulated ET-1 production in cultured human endothelial cells,16 they hypothesized that ANP mediated the decrease in urinary ET-1 in their study. As ANP and BNP have been demonstrated to act on the same receptors within the kidney,29 30 our study suggests that other factors probably mediate the decrease observed in urinary ET-1 during acute volume expansion. In fact, in our study, BNP caused an increase in urinary ET-1 concentration; therefore, it seems more probable for ANP to limit rather than cause the decrease in urinary ET-1 excretion. Nevertheless, it is possible that the increase in plasma BNP might cause intrarenal vasodilation, while the increased urinary ET-1 might lead to compensatory intrarenal vasoconstriction.
In vitro studies have shown that ANP is able to inhibit ET-1 release from endothelial cells.16 In our study, the increase in BNP plasma levels obtained during BNP infusion was similar to that observed in patients affected by heart failure31 and was not able to modify ET-1 plasma levels significantly, although a tendency toward a decrease with time was observed. It is not known whether higher doses of BNP might be able to decrease basal ET-1 plasma levels. Nevertheless, our data demonstrate that the effects exerted by cardiac natriuretic peptides on ET-1 synthesis and release are different at the level of different tissues, such as the kidney and peripheral vessels.
Urinary ET-1 excretion has also been demonstrated to change in pathological conditions.32 In uninephrectomized patients, the functional overload of the residual kidney is accompanied by an increase in urinary ET-1.33 This finding is in agreement with the increased urinary excretion of the peptide found in rats after extensive surgical ablation of renal mass.34
Urinary ET-1 excretion has been found to be decreased in essential hypertension, especially in patients whose BP is sensitive to salt loading.35 Similar results have been obtained in experimental animals. Spontaneously hypertensive rats show a decrease in inner medullary collecting duct ET-1 production,27 36 and heterozygous ET-1+/-mice, in which ET-1 production is generally decreased in either plasma or urine,37 are characterized by an increase in BP. These findings have led some authors38 to hypothesize that a decreased production in renal ET-1 might participate in the genesis of hypertension through a decrease in natriuresis. In light of the results obtained in the present study, which showed a close functional link between cardiac natriuretic peptides and urinary ET-1, it is interesting to point out that salt loading causes an impaired ANP release in salt-sensitive essential hypertensive individuals39 as well as in spontaneously hypertensive rats.40 Animal models using ET-1 antagonists will help to clarify whether a decrease in urinary ET-1 plays a role in the blunted response of ANP to salt loading observed in salt-sensitive individuals.
In conclusion, our study demonstrates that in normal humans, a close functional relationship exists between cardiac natriuretic peptides and renal ET-1 production. Whether renal ET-1 participates in the natriuretic action of cardiac natriuretic peptides in health or disease remains to be established.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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This work was partly supported by a grant from the University of Florence.
Received June 4, 1996;
first decision July 10, 1996; first decision August 8, 1996;
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References |
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1. Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yasaki Y, Goto K, Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988;332:411-415.[Medline] [Order article via Infotrieve]
2. Pupilli C, Brunori M, Misciglia N, Selli C, Ianni L, Yanagisawa M, Mannelli M, Serio M. Presence and distribution of endothelin-1 gene expression in human kidney. Am J Physiol. 1994;267:F679-F687.[Medline] [Order article via Infotrieve]
3. Kohan DE. Endothelin production by human inner medullary collecting ducts. J Am Soc Nephrol. 1993;3:1719-1721.[Medline] [Order article via Infotrieve]
4. Berbinschi A, Ketelslegers JM. Endothelin in urine. Lancet. 1989;2:46. Letter.[Medline] [Order article via Infotrieve]
5. Morita S, Kitamura K, Yamamoto Y, Eto T, Osada Y, Sumiyoshi A, Koono M, Tanaka K. Immunoreactive endothelin in human kidney. Ann Clin Biochem. 1991;28:267-271.[Medline] [Order article via Infotrieve]
6. Davenport AP, Nunez DJ, Brown MJ. Binding sites for 125I labelled endothelin-1 in the kidneys: differential distribution in rat, pig and man demonstrated by using quantitative autoradiography. Clin Sci (Colch). 1989;77:129-131.[Medline] [Order article via Infotrieve]
7. Grone H-J, Laue A, Fuchs E. Localization and quantification of [125I]-endothelin binding sites in human fetal and adult kidneys: relevance to renal ontogeny and pathophysiology. Klin Wochenschr. 1990;68:758-767.[Medline] [Order article via Infotrieve]
8. Goetz KL, Wang BC, Madwed JB, Zhu LJ, Leadley RJ Jr. Cardiovascular, renal and endocrine responses to intravenous endothelin in conscious dogs. Am J Physiol. 1988;255:R1064-R1068.[Medline] [Order article via Infotrieve]
9. King AJ, Brenner BM, Anderson S. Endothelin: a potent renal and systemic vasoconstrictor peptide. Am J Physiol. 1989;256:F397-F402.[Medline] [Order article via Infotrieve]
10. Hirata Y, Matsuoka H, Kimura K, Fukui K, Hayakawa H, Suzuki E, Sugimoto T, Yanagisawa M, Masaki T. Renal vasoconstriction by the endothelial cell-derived peptide endothelin in spontaneously hypertensive rats. Circ Res. 1989;65:1370-1379.
11. Miller WL, Redfield MM, Burnett JC. Integrated cardiac, renal and endocrine actions of endothelin. J Clin Invest. 1989;83:317-320.[Medline] [Order article via Infotrieve]
12. Garcia R, Lachance D, Thibault G. Positive inotropic action, natriuresis and atrial natriuretic factor release induced by endothelin in conscious rat. J Hypertens. 1990;8:725-731.[Medline] [Order article via Infotrieve]
13. Ferrario RG, Foulkes R, Salvati P, Patrono C. Hemodynamic and tubular effects of endothelin and thromboxane in the isolated perfused rat kidney. Eur J Pharmacol. 1988;171:127-134.
14. Nitta K, Naruse M, Sanaka T, Tsuchiya K, Naruse K, Zeng Z, Demura H, Sugino N. Natriuretic and diuretic effects of endothelin in isolated perfused rat kidney. Endocrinol Jpn. 1990;36:887-890.
15. Perico N, Dadan J, Gabanelli M, Remuzzi G. Cyclooxygenase products and atrial natriuretic peptide modulate renal response to endothelin. J Pharmacol Exp Ther. 1990;252:1213-1220.
16. Saijonmaa O, Ristimaki A, Fyhrquist F. Atrial natriuretic peptide, nitroglycerine, and nitroprusside reduce basal and stimulated endothelin production from cultured endothelial cells. Biochem Biophys Res Commun. 1990;173:514-520.[Medline] [Order article via Infotrieve]
17. Moe O, Tejedor A, Campbell WB, Alpern RJ, Henrich WL. Effects of endothelin on in vitro renin secretion. Am J Physiol. 1991;260:E521-E525.[Medline] [Order article via Infotrieve]
18. Matsumura Y, Nakase K, Ikegawa R, Hayashi K, Ohyama T, Morimoto S. The endothelium-derived vasoconstrictor peptide endothelin inhibits renin release in vitro. Life Sci. 1989;44:149-157.[Medline] [Order article via Infotrieve]
19. Takagi Y, Tsukada H, Matsuoka H, Yagi S. Inhibitory effect of endothelin on renin release in vitro. Am J Physiol. 1989;257:E833-E838.[Medline] [Order article via Infotrieve]
20. Holmes SJ, Espiner EA, Richards AM, Yandle TG, Frampton C. Renal, endocrine and hemodynamic effects of human brain natriuretic peptide in normal men. J Clin Endocrinol Metab. 1993;76:91-96.[Abstract]
21. La Villa G, Vena S, Conti A, Fronzaroli C, Bratt A, Lazzeri C, Tosti-Guerra C, Madiai S, Marra N, Franchi F. Plasma levels of brain natriuretic peptide in healthy subjects and patients with essential hypertension: response to posture. Clin Sci. 1993;85:411-416.[Medline] [Order article via Infotrieve]
22. Pinzani M, Milani S, De Frames R, Grappone C, Caligiuri A, Gentilini A, Tosti Guerra C, Maggi M, Failli P, Gentilini P. ET-1 is overexpressed in human cirrhotic liver and exerts multiple effects on activated hepatic stellate cells. Gastroenterology. 1996;110:534-548.[Medline] [Order article via Infotrieve]
23. Simonson MS. Endothelins: multifocal renal peptides. Physiol Rev. 1993;73:375-411.
24. Abassi ZA, Tate JE, Golomb E, Keiser HR. Role of neutral endopeptidase in the metabolism of endothelin. Hypertension. 1992;20:89-95.
25. Neri Serneri GG, Modesti PA, Cecioni I, Biagini D, Migliorini A, Costoli A, Colella A, Naldoni A, Paoletti P. Plasma endothelin and renal endothelin are two distinct systems involved in volume homeostasis. Am J Physiol. 1995;268:H1829-H1837.[Medline] [Order article via Infotrieve]
26. Wilkes BM, Susin M, Mento PF, Macica CM, Girardi EP, Boss E, Nord P. Localization of endothelin-like immunoreactivity in rat kidneys. Am J Physiol. 1991;260:F913-F920.[Medline] [Order article via Infotrieve]
27. Kitamura K, Tanaka T, Kato J, Ogawa T, Eto T, Tanaka K. Immunoreactive endothelin in rat kidney inner medulla: marked decrease in spontaneously hypertensive rats. Biochem Biophys Res Commun. 1989;162:38-44.[Medline] [Order article via Infotrieve]
28. Modesti PA, Cecioni I, Naldoni A, Migliorini A, Neri Serneri GG. Relationship of renin-angiotensin system and ET-1 system activation in long-lasting response to postural changes. Am J Physiol. 1996;270:H1200-H1206.[Medline] [Order article via Infotrieve]
29. Sudoh T, Kangawa K, Minamino N, Matsuo H. A new natriuretic peptide in porcine brain. Nature. 1988;332:78-81.[Medline] [Order article via Infotrieve]
30. Kohno M, Yokokawa K, Mandai AK, Horio T, Yasunari K, Takeda T. Cardiac natriuretic peptides inhibit cyclosporine-induced production of endothelin in cultured rat mesangial cells. Metabolism. 1995;44:404-409.[Medline] [Order article via Infotrieve]
31. Mukoyama M, Nakao K, Hosoda K, Suga S, Saito Y, Ogawa Y, Shirakami G, Jougasaki M, Obata K, Yasue H, Kambayashi Y, Inouye K, Imura H. Brain natriuretic peptide as a novel cardiac hormone in humans. J Clin Invest. 1991;87:1402-1412.[Medline] [Order article via Infotrieve]
32. Remuzzi G, Benigni A. Endothelins in the control of cardiovascular and renal function. Lancet. 1993;342:589-593.[Medline] [Order article via Infotrieve]
33. Takeda M, Komeyama T, Tsutsui T, Mizusawa T, Go H, Tamaki M, Hatano A. Changes in urinary excretion of endothelin-1-like immunoreactivity before and after unilateral nephrectomy in humans: comparison with other urinary parameters and unilateral adrenalectomy. Nephron. 1994;67:180-184.[Medline] [Order article via Infotrieve]
34. Benigni A, Perico N, Gaspari F, Zoja C, Bellizzi L, Gabanelli M, Remuzzi G. Increased renal endothelin production in rats with reduced renal mass. Am J Physiol. 1991;260:F331-F339.[Medline] [Order article via Infotrieve]
35. Hoffman A, Grossman E, Goldstein DS, Gill JR Jr, Keiser HR. Urinary excretion rate of endothelin-1 in patients with essential hypertension and salt sensitivity. Kidney Int. 1994;45:556-560.[Medline] [Order article via Infotrieve]
36. Hughes AK, Cline RC, Kohan DE. Alterations in renal endothelin-1 production in the spontaneously hypertensive rat. Hypertension. 1992;20:666-673.
37. Kurihara Y, Kurihara H, Suzuki H, Kodama T, Maemura K, Nagai R, Oda H, Kuwaki T, Cao WH, Kamada N, Jishage K, Ouchi Y, Azuma S, Toyoda Y, Ishikawa T, Kumada M, Yazaki Y. Elevated blood pressure and craniofacial abnormalities in mice deficient in endothelin-1. Nature. 1994;368:703-710.[Medline] [Order article via Infotrieve]
38. Hoffman A, Grossman E, Abassi Z, Keiser HR. Renal endothelin and hypertension. Nature.. 1994;372:50. Letter.[Medline] [Order article via Infotrieve]
39. Niimura S. Attenuated release of atrial natriuretic factor due to sodium loading in salt-sensitive essential hypertension. Jpn Heart J. 1991;32:167-180.[Medline] [Order article via Infotrieve]
40. Jin H, Chen YF, Yang RH, Meng QC, Oparil S. Impaired release of atrial natriuretic factor in NaCl-loaded spontaneously hypertensive rats. Hypertension. 1988;11:739-744.
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