Skip to main content
Log in

Renal blood flow control by tubuloglomerular feedback (TGF) in normal and spontaneously hypertensive rats — a role for dopamine and adenosine

  • Published:
Klinische Wochenschrift Aims and scope Submit manuscript

Summary

Following the elementary laws of hemodynamics and the functional characteristics of the renal myogenic and macula densa-mediated (TGF) vascular resistance control mechanisms, TGF-mediated changes of renal vascular resistance are amplified by cooperative changes of the myogenic mechanism. Myogenically induced changes, on the other hand, would be antagonized by TGF. Resetting of renal vascular flow resistance by alterations to the TGF mechanisms might thus be more effective than alterations to the myogenic mechanism. Dopamine and adenosine, two autacoids occurring normally in the tubular fluid, may play a key role in operating such a resetting mechanism. Dopamine and adenosine were found in proximal tubular fluid at concentrations of 10−8 and 0.5 10−6 M respectively. Dopamine inhibits the tubuloglomerular feedback mechanism, this inhibition is antagonized concentration-dependently by adenosine. These effects most likely occur via D1 and A1 receptors and hence by regulation of the adenyl cyclase activity in the macula densa cells. The balance between adenosine and dopamine in tubular fluid appears to be under the control of extrarenal parameters. In normal rats, high dietary salt intake, by influencing the secretion of an unknown adrenal hormone, and inhibition of Na-K-ATPase might be of importance. In spontaneously hypertensive rats unknown genetic parameters may also play a role.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

TGF:

tubuloglomerular feedbackmechanism

SFP:

stopped flow pressure

SNGFR:

Single nephron glomerular filtration rate

ATF:

Artifical proximal tubular fluid

TF:

Tubular fluid

ADX:

Acutely Adrenalectomized

SHR:

Spontaneous hypertensive Rat

KW:

Kidney weight

ANO-VA:

Analysis of variance

“EC50”:

Half-maximal activity

HPLC:

High performance liquid chromatography

References

  1. Angielski S, Le-Hir M, Dubach UC (1983) Transport of adenosine by renal brush border membranes. Pflügers Arch 397:75–77

    Google Scholar 

  2. Angielski S, Redlak M, Szczepanska-Konkel M (1990) Intrarenal adenosine prevents hyperfiltration induced by atrial natriuretic factor. Miner Electrolyte Metab 16:57–60

    Google Scholar 

  3. Arend LJ, Thompson CI, Spielman WS (1985) Dipyridamole decreases glomerular filtration in the sodium-depleted dog. Evidence for mediation by intrarenal adenosine. Circ Res 56:242–251

    Google Scholar 

  4. Baines AD, Drangova R (1984) Dopamine production by the isolated perfused rat kidney. Can J Physiol Pharmacol 62:272–276

    Google Scholar 

  5. Baines AD, Drangova R (1986) Neural not tubular dopamine increases glomerular filtration rate in perfused rat kidneys. Am J Physiol 250:F674-F679

    Google Scholar 

  6. Ball SG, Gunn IG, Douglas IH (1982) Renal handling of dopa, dopamine, norepinephrine, and epinephrine in the dog. Am J Physiol 242:F56-F62

    Google Scholar 

  7. Beach RE, DeBose TD Jr (1990) Adrenergic regulation of (Na+, K+)-ATPase activity in proximal tubules of spontaneously hypertensive rats. Kidney Int 38:402–408

    Google Scholar 

  8. Bell PD (1985) Cyclic AMP-calcium interaction in the transmission of tubuloglomerular feedback signals. Kidney Int 28:728–732

    Google Scholar 

  9. Briggs JP, Schnermann J (1986) Macula densa control of renin secretion and glomerular vascular tone: evidence for common cellular mechanisms. Renal Physiol 9:193–203

    Google Scholar 

  10. Casellas D, Moore LC (1990) Autoregulation and tubuloglomerular feedback in juxtamedullary glomerular arterioles. Am J Physiol 258: F660-F669

    Google Scholar 

  11. Coulson R, Baraniak J, Stec WJ, Jastorff B (1983) Transport and metabolism of N6- and C8-substituted analogs of adenosine 3′,5′-cyclic monophosphate and adenosine 3′5′-cyclic phosphorothioate by the isolated perfused rat kidney. Life Sci 32:1489–1498

    Google Scholar 

  12. Davis JM, Takabatake T, Häberle DA (1988) The influence of renal autoregulation on TGF control of glomerular filtration rate. In: Persson AEG, Boberg U (eds) The juxtaglomerular apparatus and the tubuloglomerular feedback mechanism. Elsevier, Amsterdam, p 393

    Google Scholar 

  13. Davis JM, Takabatake T, Kawata T, Häberle DA (1988) Resetting of tubuloglomerular feedback in acute volume expansion in rats. Pflügers Arch 411:322–327

    Google Scholar 

  14. Dawson TP, Gandhi R, Le-Hir M, Kaissling B (1989) Ecto-5′-nucleotidase: localization in rat kidney by light microscopic histochemical and immunohistochemical methods. J Histochem Cytochem 37:39–47

    Google Scholar 

  15. Dietz R, Schomig A, Rascher W, Strasser R, Kubler W (1980) Enhanced sympathetic activity caused by salt loading in spontaneously hypertensive rats. Clin Sci 59 (Suppl 6): 171s-173s

    Google Scholar 

  16. Ebeling PR, Adam WR, Moseley JM, Martin TJ (1989) Actions of synthetic parathyroid hormone-related protein (1–34) on the isolated rat kidney. J Endocrinol 120:45–50

    Google Scholar 

  17. Felder RA, Seikaly MG, Cody P, Eisner GM, Jose PA (1990) Attenuated renal response to dopaminergic drugs in spontaneously hypertensive rats. Hypertension 15: Part 1, 56

    Google Scholar 

  18. Franco M, Bell PD, Navar LG (1989) Effect of adenosine A1 analogue on tubuloglomerular feedback mechanism. Am J Physiol 257:F231-F236

    Google Scholar 

  19. Grangsjö G, Wolgast M (1972) The pressure flow relationship in renal cortical and medullary circulation. Acta Physiol Scand 85:228

    Google Scholar 

  20. Hagege J, Richet G (1985) Proximal tubule dopamine histofluorescence in renal slices incubated with L-dopa. Kidney Int 27:3–8

    Google Scholar 

  21. Hayashi M, Yamaji Y, Kitajima W, Saruta T (1990) Aromatic L-amino acid decarboxylase activity along the rat nephron. Am J Physiol 258:F28-F33

    Google Scholar 

  22. Häberle DA (1988) Hemodynamic interactions between intrinsic blood flow control mechanisms in the rat kidney. Renal Physiol Biochem 11:289–315

    Google Scholar 

  23. Häberle DA, Davis JM (1984) Resetting of tubuloglomerular feedback: evidence for a humoral factor in tubular fluid. Am J Physiol 246:F495-F500

    Google Scholar 

  24. Häberle DA, Königbauer B (1991) Inhibition of tubuloglomerular feedback by the D1-agonist Fenoldopam in chronically salt loaded rats. J Physiol (London) (in press)

  25. Häberle DA, Königbauer B (1991) Chronic dietary salt loading: resetting of tubuloglomerular feedback control of renal hemodynamics by an adrenal hormone. Kidney Int (in press)

  26. Häberle DA, Davis JM, Kawata T, Dahlheim H, Schmitt E (1988) The effect of adrenalectomy on the resetting of tubuloglomerular feedback in chronic volume expansion. In: Persson AEG, Boberg U (eds) The juxtaglomerular apparatus and the tubuloglomerular feedback mechanism. 11th edn. Elsevier, Amsterdam, p 177

    Google Scholar 

  27. Häberle DA, Königbauer B, Davis JM, Kawata T, Mast C, Metz C, Dahlheim H (1990) Autoregulation of the glomerular filtration rate and the single-nephron glomerular filtration rate despite inhibition of tubuloglomerular feedback in rats chronically volume-expanded by deoxycorticosterone acetate. Pflügers Arch 416:548–553

    Google Scholar 

  28. Häberle DA, Königbauer B, Stachl M, Häuser W, Becker BF, Dominiak P (1991) Intrinsic control of tubuloglomerular feedback: antagonism between endogenous adenosine and dopamine in tubular fluid. Pflügers Arch (in press)

  29. Herlitz H, Lundin S, Henning M, Aurell M, Karlberg BE, Berglund G (1982) Hormonal pattern during development of hypertension in spontaneously hypertensive rats (SHR). Clin Exp Hypertens [A] 4:915–935

    Google Scholar 

  30. Johnson PC (1980) The myogenic response. In: Bohr DF, Somlyo AP, Sparks HV (eds) Handbook of physiology, section 2, the cardiovascular system, Vol II: Vascular smooth muscle. Am Physiol Soc, Bethesda, p 409

    Google Scholar 

  31. Johnson PC, Intaglietta M (1976) Contributions of pressure and flow sensitivity to autoregulation in mesenteric arterioles. Am J Physiol 231:1686–1698

    Google Scholar 

  32. Joppich R, Schrader J, Häberle DA (1980) Effect of antidiuretic hormone and dibutyryl cAMP upon the urinary concentrating capacity in neonatal piglets. Pediatr Res 14:1234–1237

    Google Scholar 

  33. Katholi RE, McCann WP, Woods WT (1985) Intrarenal adenosine produces hypertension via renal nerves in the one-kidney, one clip rat. Hypertension 8:188–193

    Google Scholar 

  34. Katholi RE, Creek RD, McCann WP (1988) Endogenous intrarenal adenosine preserves renal blood flow in one-kidney, one clip rats. Hypertension 11:651–656

    Google Scholar 

  35. Kawata T, Davis JM, Königbauer B, Häberle DA (1991) The effect of nitrendipine on autoregulation, tubuloglomerular feedback, electrolyte excretion and Li-clearance in the rat kidney. J Physiol (London) (submitted for publication)

  36. Källskog Ö, Lindbom LO, Ulfendahl HR, Wolgast M (1975) The pressure flow relationship of different nephron populations in the rat. Acta Physiol Scand 94:289–300

    Google Scholar 

  37. Källskog Ö, Lindbom LO, Ulfendahl HR, Wolgast M (1976) Hydrostatic pressures within the vascular structures of the rat kidney. Pflügers Arch 363:205–210

    Google Scholar 

  38. Kinoshita S, Sidhu A, Felder RA (1989) Defective dopamine-1 receptor adenylate cyclase coupling in the proximal convoluted tubule from the spontaneously hypertensive rat. J Clin Invest 84:1849–1856

    Google Scholar 

  39. Kuttesch JF Jr, Robins MJ, Nelson JA (1982) Renal transport of 2′-deoxytubercidin in mice. Biochem Pharmacol 31:3387–3394

    Google Scholar 

  40. McGrath B, Bode K, Luxford A, Howden B, Jablonski P (1985) Effects of dopamine on renal function in the rat isolated perfused kidney. Clin Exp Pharmacol Physiol 12:343–352

    Google Scholar 

  41. Miller W, Thomas RA, Berne RM, Rubio R (1978) Adenosine production in the ischemic kidney. Circ Res 43:390–397

    Google Scholar 

  42. Nelson JA, Kuttesch JR Jr, Herbert BH (1983) Renal secretion of purine nucleosides and their analogs in mice. Biochem Pharmacol 32:2323–2327

    Google Scholar 

  43. Oates NS, Ball SG, Perkins CM, Lee MR (1979) Plasma and urine dopamine in man given sodium chloride in the diet. Clin Sci 56:261–264

    Google Scholar 

  44. Osswald H, Schmitz H-J, Heidenreich O (1975) Adenosine response of the rat kidney after saline loading, sodium restriction and hemorrhagia. Pflügers Arch 357:323–333

    Google Scholar 

  45. Rennick BR (1968) Dopamine: renal tubular transport in the dog and plasma binding studies. Am J Physiol 215:532–534

    Google Scholar 

  46. Schnermann J (1988) Effect of adenosine analogues on tubuloglomerular feedback responses. Am J Physiol 255:F33-F42

    Google Scholar 

  47. Schnermann J, Briggs JP (1985) Function of juxtaglomerular apparatus: local control of glomerular hemodynamics. In: Seldin DW, Giebisch G (eds) The Kidney: physiology and pathophysiology. 1st edn. Raven Press, New York, p 669

    Google Scholar 

  48. Schnermann J, Schubert G, Hermle M, Herbst R, Stowe NT, Yarimizu S, Weber PC (1979) The effect of inhibition of prostaglandin synthesis on tubuloglomerular feedback in the rat kidney. Pflügers Arch 379:269–286

    Google Scholar 

  49. Schnermann J, Schubert G, Briggs J (1986) Tubuloglomerular feedback responses with native and artificial tubular fluid. Am J Physiol 250:F16-F21

    Google Scholar 

  50. Spielman WS, Thompson CI (1982) A proposed role for adenosine in the regulation of renal hemodynamics and renin release. Am J Physiol 242:F423-F435

    Google Scholar 

  51. Suzuki H, Nakane H, Kawamura M, Yoshizawa M, Takeshita E, Saruta T (1984) Excretion and metabolism of dopa and dopamine by isolated perfused rat kidney. Am J Physiol 247:E285-E290

    Google Scholar 

  52. Thompson CI, Sparks HV, Spielman WS (1985) Renal handling and production of plasma and urinary adenosine. Am J Physiol 248:F545-F551

    Google Scholar 

  53. Unger T, Buu NT, Kuchel O, Schurch W (1980) Conjugated dopamine: peripheral origin, distribution, and response to acute stress in the dog. Can J Physiol Pharmacol 58:22–27

    Google Scholar 

  54. Ushiogi Y, Takabatake T, Häberle DA (1991) Salt sensitivity of blood pressure and attenuation of tubuloglomerular feedback mechanism in chronically salt-loaded spontaneous hypertensive rats. Kidney Int (in press)

  55. Wahbe F, Hagege J, Loreau N, Ardaillou R (1982) Endogenous dopamine synthesis and dopa-decarboxylase activity in rat renal cortex. Mol Cell Endocrinol 27:45–54

    Google Scholar 

  56. Weihprecht H, Lorenz JN, Schnermann J, Skott O, Briggs JP (1990) Effect of adenosine 1-receptor blockade on renin release from rabbit isolated perfused juxtaglomerular apparatus. J Clin Invest 85:1622–1628

    Google Scholar 

  57. Yoshimura M, Kambara S, Takahasi H, Okabayashi H, Ijichi H (1987) Involvement of dopamine in development of hypertension in the spontaneously hypertensive rat: effect of carbidopa, inhibitor of peripheral dopa decarboxylase. Clin Exp Hypertens [A] 9:1585–1599

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Preprint of a lecture to be read at the 22nd Congress of the “Gesellschaft für Nephrologie”, Heidelberg, September 15–18, 1991 (Editor: Prof. Dr. E. Ritz, Heidelberg)

Supported by Deutsche Forschungsgemeinschaft Ha 775/9-2, 11-1

Rights and permissions

Reprints and permissions

About this article

Cite this article

Häberle, D.A., Königbauer, B., Kawabata, M. et al. Renal blood flow control by tubuloglomerular feedback (TGF) in normal and spontaneously hypertensive rats — a role for dopamine and adenosine. Klin Wochenschr 69, 587–596 (1991). https://doi.org/10.1007/BF01649321

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01649321

Key words

Navigation