Advertisement

Pflügers Archiv

, Volume 427, Issue 1–2, pp 42–46 | Cite as

Role of the macula densa in the control of renal renin gene expression in two-kidney/one-clip rats

  • Karin Schricker
  • Marlies Hamann
  • Brigitte Kaissling
  • Armin Kurtz
Transport Processes, Metabolism and Endocrinology; Kidney, Gastrointestinal Tract, and Exocrine Glands

Abstract

This study was designed to examine whether macula densa function is involved in the changes of renal renin gene expression upon acute hypoperfusion of one kidney. To block macula densa function, rats with free access to salt and water were subcutaneously infused with furosemide (12 mg/day) for 6 days. Then, 4 days after the start of the infusion, the left renal arteries were clipped with 0.2-mm silver clips and renin mRNA levels in ipsilateral and contralateral kidneys, as well as plasma renin activities (PRA), were determined 48 h after clipping. In non-clipped animals furosemide increased PRA from 10 to 47 ng angiotensin I · h−1 · ml−1 and raised renin mRNA levels in both kidneys 2.5-fold. In vehicle-infused animals, clipping of the left renal artery increased PRA to 37 ng angiotensin I · h−1 · ml−1 and led to a 5-fold rise of renin mRNA levels in the ipsilateral kidneys and to a suppression to 20% of the control values in the contralateral kidneys. PRA values in clipped and furosemide-infused animals were 45 ng angiotensin I · h−1 · ml−1. In these animals renin mRNA levels increased in the ipsilateral kidneys to similar absolute values as in vehicle-infused rats, whilst contralateral renin mRNA levels fell to about 25% of the respective controls. These findings indicate that the stimulations of renin gene expression by inhibition of macula densa salt transport and by renal artery clipping are not additive, suggesting that the macula densa mechanism may participate in the stimulation of renin gene expression upon hypoperfusion. The macula densa mechanism, however, appears to be not essentially involved in the suppression of renin gene expression in the contralaterals to stenosed kidneys.

Key words

Furosemide Juxtaglomerular cells Renin secretion 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Barrett GL, Morgan TO, Alcorn D (1990) Stimulation of renin synthesis in the hydronephrotic kidney during sodium depletion. Pflügers Arch 415:774–776Google Scholar
  2. 2.
    Burnham CE, Hawelu-Johnson CL, Frank BM, Lynch KR (1987) Molecular cloning of rat renin cDNA and its gene. Proc Natl Acad Sci USA 84:5605–5609Google Scholar
  3. 3.
    Chen M, Schnerman J, Malvan RL, Killen PD, Briggs JP (1993) Time course of stimulation of renal renin m-RNA by furosemide. Hypertension 21:36–41Google Scholar
  4. 4.
    Chomczynski P, Sacchi N (1986) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159Google Scholar
  5. 5.
    Holmer H, Eckhardt KU, Aedtner O, LeHir M, Schricker K, Hamann M, Götz KH, Riegger G, Moll W, Kurtz A (1993) Which factor mediates reno-renal control of renin gene expression? J Hypertens (in press)Google Scholar
  6. 6.
    Ingelfinger JR, Pratt RE, Ellison K, Dzau VJ (1986) Sodium regulation of angiotensinogen mRNA expression in rat kidney cortex and medulla. J Clin Invest 78:1311–1315Google Scholar
  7. 7.
    Johns DW, Peach MJ, Gomez RA, Inagami T, Carey RM (1990) Angiotensin II regulates renin gene expression. Am J Physiol 259:F882-F887Google Scholar
  8. 8.
    Kaissling B, Stanton BA (1988) Adaptation of distal tubule and collecting duct to increased sodium delivery. I. Ultrastructure. Am J Physiol 255:F1256-F1268Google Scholar
  9. 9.
    Keeton K, Campbell WB (1981) The pharmacologic alteration of renin release. Pharmacol Rev 31:81–227Google Scholar
  10. 10.
    Kohara K, Broshihan KB, Ferrario CM, Milsted A (1992) Peripheral and central angiotensin II regulates expression of genes of the renin-angiotensin system. Am J Physiol 262:E651-E657Google Scholar
  11. 11.
    Lorenz JN, Weihprecht H, Schnermann J, Skott O, Briggs JP (1991) Renin release from isolated juxtaglomerular apparatus depends on macula densa chloride transport. Am J Physiol 260:F486-F493Google Scholar
  12. 12.
    Ludwig G, Ganten D, Murakami K, Fasching U, Hackenthal E (1987) Relationship between renin mRNA and renin secretion in adrenalectomized, salt depleted or converting enzyme inhibitor-treated rats. Mol Cell Endocrinol 50:223–229Google Scholar
  13. 13.
    Makrides SC, Mulinari R, Zannis VI, Gavras H (1988) Regulation of renin gene expression in hypertensive rats. Hypertension 12:405–410Google Scholar
  14. 14.
    Modena B, Hohner S, Eckhardt KU, Schricker K, Riegger G, Kaissling B, Kurtz A (1993) Furosemide stimulates renin expression in the kidneys of salt balanced rats. Pflügers Arch (in press)Google Scholar
  15. 15.
    Moffett RB, McGowan RA, Gross KW (1986) Modulation of kidney renin messenger RNA levels during experimentally induced hypertension. Hypertension 8:874–882Google Scholar
  16. 16.
    Nakamura A, Iwao H, Fukui K, Kimura S, Tamaki T, Nakanishi S, Abe Y (1990) Regulation of liver angiotensinogen and kidney renin mRNA levels by angiotensin II. Am J Physiol 258:E1-E6Google Scholar
  17. 17.
    Ploth DW (1983) Angiotensin-dependent renal mechanisms in two-kidney one-clip renal vascular hypertension. Am J Physiol 245:F131-F141Google Scholar
  18. 18.
    Ratcliffe PJ, Jones RW, Philipps RE, Nicholls LG, Bell JI (1990) Oxygen-dependent modulation of erythropoietin mRNA levels in isolated rat kidneys studied by RNase protection. J Exp Med 172:657–660Google Scholar
  19. 19.
    Samani MJ, Godfrey MJ, Major JS, Brammar WJ, Swales JD (1989) Kidney renin m-RNA levels in the early and chronic phases of two kidney, one-clip hypertension in the rat. J Hypertens 7:105–112Google Scholar
  20. 20.
    Scholz H, Vogel U, Kurtz A (1993) Interrelation between baroreceptor and macula densa mechanisms in the control of renin secretion. J Physiol (Lond) (in press)Google Scholar
  21. 21.
    Schunkert H, Ingelfinger JR, Jacob H, Jackson B, Bouyounes H, Dzau VJ (1992) Reciprocal feed back regulation of kidney angiotensinogen and renin mRNA expression by angiotensin II. Am J Physiol 263:E863-E869Google Scholar
  22. 22.
    Vander AJ (1967) Control of renin release. Physiol Rev 47:359–382Google Scholar
  23. 23.
    Wilcox CS, Mitch WE, Kelly RA, Friedman PA, Souney P, Rayment CM, Meyer TW, Skorecki K (1984) Factors affecting potassium balance during furosemide administration. Clin Sci 67:196–203Google Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Karin Schricker
    • 1
  • Marlies Hamann
    • 1
  • Brigitte Kaissling
    • 2
  • Armin Kurtz
    • 1
  1. 1.Physiologisches Institut der Universität RegensburgRegensburgGermany
  2. 2.Anatomisches Institut der Universität ZürichSwitzerland

Personalised recommendations