Abstract
Background/Aims: High atrial natriuretic peptide (ANP) serum levels are seen in acute renal failure (ARF) due to impaired ANP clearance, but the response of ANP to blood volume expansion is blunted. ARF-associated hypothyroidism influences ANP clearance but it may also play a role in the synthesis and release of ANP because in primary hypothyroidism both mechanisms are disturbed. The aim of this study is to analyze whether thyroxin (T4) supplementation improves the synthesis and release of ANP in ARF. Methods: Four groups of rats were studied: group C (control); group ARF; Group ARF-T4 (ARF supplemented with T4), and group Tx (thyroidectomized). Serum creatinine (SCr), creatinine clearance (CrCl), total T4, total triiodothyronin (T3), plasma ANP, ANP response to acute saline load and atrial content of mRNA-ANP were measured 5 days after ARF induction with potassium dichromate. Results: CrCl was 1.8 ± 0.4 ml/min in group C, and it significantly dropped to 0.6 ± 0.5 in ARF (p < 0.01), T4 improved it (1.7 ± 0.7 in ARF-T4, p < 0.01) and Tx did not change it. Plasma ANP was higher in ARF as compared with C (152 ± 23 vs. 52 ± 21 fmol/l, p < 0.01). In ARF-T4, ANP was higher than in C but lower than in ARF (85 ± 28 fmol/l, p < 0.01). No changes were observed in Tx rats (48 ± 17 fmol/l). The atrial content of mRNA-ANP was 0.06 ± 0.025 mRNA-ANP/mRNA-β-actin ratio units in group C, it was higher in ARF (0.13 ± 0.025, p < 0.01) and lower in Tx (0.04 ± 0.01, p < 0.05) as compared to C. Supplementation with T4 increased the mRNA-ANF content (0.18 ± 0.2 mRNA-ANP/mRNA-β-actin ratio units, p < 0.05) over ARF. Plasma ANP response to saline load was 45 ± 7% in C, but it was reduced in ARF and Tx (20 ± 10 and 26 ± 10%, p < 0.01). In ARF-T4 the response was restored (36 ± 9%, p < 0.01 vs. ARF). Conclusion: Thyroid hormones modulate the synthesis and release of ANP in ARF. Although the effect is probably direct, T4-induced amelioration of renal damage may also play a significant role by improving the uremic milieu.
Journal Section:
Original Paper
References
1.
Liano F, Pascual J: Outcomes in acute renal failure. Semin Nephrol 1998;18:541–550.
[PubMed]
2.
Obialo CI, Okonofua EC, Tayade AS, Riley LJ: Epidemiology of the novo acute renal failure in hospitalized African Americans: Comparing community-acquired vs hospital-acquired disease. Arch Intern Med 2000;160:1309–1313.
3.
Schramm L, Heidbreder E, Lukes M, Weierich T, Lopau K, Zimmermann J, Wanner C: Endotoxin-induced acute renal failure in the rat: Effects of urodilatin and diltiazem on renal function. Clin Nephrol 1996;46:117–124.
[PubMed]
4.
Heidbreder E, Schafferhans K, Aktas N, Heyd-Schramm A, Heidland A: Toxic acute renal failure of rats: Effects of atrial natriuretic peptide on renal function; in Brenner BM, Laragh JH (eds): Advances in Atrial Peptide Research. New York, Raven Press, 1988, pp 375–380.
5.
Schafferhans K, Heidbreder E, Sperber S, Dämmrich J, Heidland A: Renal actions of atrial natriuretic peptide in gentamicin-induced acute renal failure; in Brenner BM, Laragh JH (eds): Advances in Atrial Peptide Research. New York, Raven Press, 1988, pp 381–385.
6.
Lewis J, Salem MM, Chertow GM, Weisberg LS, McGrew F, Marbury TC, Allgren RL: Atrial natriuretic factor in oliguric acute renal failure. Anaritide Acute Renal Failure Study Group. Am J Kidney Dis 2000;36:767–774.
[PubMed]
7.
Meyer M, Pfarr E, Schirmer G, Uberbacher HJ, Schope K, Bohm E, Fluge T, Mentz P, Scigalla P, Forssmann WG: Therapeutic use of the natriuretic peptide ularitide in acute renal failure. Ren Fail 1999;21:85–100.
[PubMed]
8.
Kurnik BR, Allgren RL, Genter FC, Solomon RJ, Bates ER, Weisberg LS: Prospective study of atrial natriuretic peptide for the prevention of radiocontrast-induced nephropathy. Am J Kidney Dis 1998;31:674–680.
[PubMed]
9.
Paniagua R, Franco M, Rodríguez E, Sánchez G, Morales G, Herrera-Acosta J: Impaired atrial natriuretic factor systemic clearance contributes to its higher levels in uremia. J Am Soc Nephrol 1992;2:1704–1708.
10.
Kohno M, Takaori K, Matsuura T, Murakawa K, Kanayama Y, Takeda T: Atrial natriuretic polypeptide in atria and plasma in experimental hyperthyroidism and hypothyroidism. Biochem Biophys Res Commun 1986;134:178–183.
11.
Ladenson PW, Langevin H, Michener M: Plasma atriopeptin concentrations in hyperthyroidism, euthyroidism, and hypothyroidism: Studies in man and rat. J Clin Endocrinol Metab 1987;65:1172–1176.
12.
Bernstein R, Midtbo K, Urdal P, Morkrid L, Smith G, Muller C, Bjoro T, Haug E: Serum N-terminal pro-atrial natriuretic factor 1-98 before and during thyroxin replacement therapy in severe hypothyroidism. Thyroid 1997;7:415–419.
[PubMed]
13.
Diekman MJ, Harms MP, Endert E, Wieling W, Wiersinga WM: Endocrine factors related to changes in total peripheral vascular resistance after treatment of thyrotoxic and hypothyroid patients. Eur J Endocrinol 2001;144:339–346.
14.
Seiken G, Grillo FG, Schaudies RP, Johnson JP: Modulation of renal EGF in dichromate-induced acute renal failure treated with thyroid hormone. Kidney Int 1994;45:1622–1627.
15.
Siegel NJ, Gaudio KM, Katz LA, Reilly HF, Ardito TA, Hendler FG, Kashgarian M: Beneficial effect of thyroxin on recovery from toxic acute renal failure. Kidney Int 1984;25:906–911.
16.
Kokot F, Grzeszczak W, Zukowska-Szczechowska E, Wiecek A: Water immersion-induces alterations of plasma atrial natriuretic peptide level and its relationship to the renin-angiotensin-aldosterone system and vasopressin secretion in acute and chronic renal failure. Clin Nephrol 1989;31:247–252.
17.
Bratusch-Marrain P, Vierhapper H, Grubeck-Loebenstein B, Waldhausl W, Kleinberger G: Pituitary-thyroid dysfunction in severe non-thyroidal disease: ‘Low-T4 syndrome’. Endokrinologie 1982;80:207–212.
18.
De Groot LJ: Dangerous dogmas in medicine: The nonthyroidal illness syndrome. J Clin Endocrinol Metab 1999;84:151–164.
[PubMed]
19.
Kanfer A, Dussaule JC, Czekalski S, Rondeau E, Sraer JD, Ardaillou R: Physiological significance of increased levels of endogenous atrial natriuretic factor in human acute renal failure. Clin Nephrol 1989;32:51–56.
20.
Ladenson, PW, Bloch KD, Seidman JG: Modulation of atrial natriuretic factor by thyroid hormone: Messenger ribonucleic acid and peptide levels in hypothyroid, euthyroid, and hyperthyroid rat atria and ventricles. Endocrinology 1988;123:652–657.
21.
Mori Y, Nishikawa M, Matsubara H, Takagi T, Toyoda N, Oikawa S, Inada M: Stimulation of rat atrial natriuretic peptide (rANP) synthesis by triiodothyronin and thyroxin: T4 as a prohormone in synthesizing rANP. Endocrinology 1990;126:466–471.
22.
Mori Y, Nishikawa M, Matsubara H, Toyoda N, Masaki H, Yonemoto T, Takagi H, Inada M: Regulation of atrial natriuretic hormone production by triiodothyronine in cultured rat atrial myocytes. Acta Endocrinol (Copenh) 1991;125:694–699.
23.
Wong NL, Huang D, Guo NS, Wong EF, Hu DC: Effects of thyroid status on atrial natriuretic peptide release from isolated rat atria. Am J Physiol 1989;256:E64–E67.
24.
Fullerton MJ, Stuchbury S, Krozowski ZS, Funder JW: Altered thyroidal status and the in vivo synthesis of atrial natriuretic peptide in the rat heart. Mol Cell Endocrinol 1990;69:227–233.
25.
Zamir N, Haass M, Keiser HR, Ohman KP: Hypophysectomy attenuates acute volume expansion-induced release of atrial natriuretic peptides from cardiac atria; in Brenner BM, Laragh JH (eds): Advances in Atrial Peptide Research. New York, Raven Press, 1988, pp 289–292.
26.
Ohman KP, Keiser HR, Zamir N: Circulating atrial natriuretic peptides in rats with experimentally induced hypo- and hyperthyroidism; in Brenner BM, Laragh JH (eds): Advances in Atrial Peptide Research. New York, Raven Press, 1988, pp 297–300.
27.
Schiffrin EL, Gutkowska J, Kuchel O, Cantin M, Genest J: Plasma concentration of atrial natriuretic factor in patients with paroxysmal atrial tachycardia. N Engl J Med 1985;312:1196–1197.
28.
Straub E: Effects of l-thyroxin in acute renal failure. Res Exp Med 1976;168:81–87.
29.
Vesely DL, San Miguel GI, Hassan I, Gower WR Jr, Schocken DD: Atrial natriuretic hormone, vessel dilator, long-acting natriuretic hormone, and kaliuretic hormone decrease the circulating concentrations of total and free T4 and free T3 with reciprocal increase in TSH. J Clin Endocrinol Metab 2001;86:5438–5442.
[PubMed]
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