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Nephrology pp 718-730 | Cite as

Role of Intracellular Calcium in the Regulation of Renal Hemodynamics

  • L. Gabriel Navar
  • Pamela K. Carmines
  • Kenneth D. Mitchell
  • P. Darwin Bell

Summary

Intracellular calcium contributes to renal hemodynamic regulatory mechanisms in multiple ways. Calcium channel blockers elicit a selective vasodilation of preglomerular arterioles leading to increases in renal blood flow (RBF), glomerular filtration rate (GFR), and glomerular pressure, with marked attenuation of autoregulatory capability. The effects of these agents seem to be restricted to the component of renal vascular resistance responsible for autoregulation and contrast with other agents which vasodilate the kidney at arterial pressures below, as well as within, the auto-regulatory range. This component of renal vascular resistance that is not influenced by calcium entry blockade can be altered by angiotensin converting enzyme inhibition. Studies at the microvascular level have demonstrated that the effects of angiotensin II on afferent arterioles are dependent upon calcium entry whereas the vasoconstrictor actions on efferent arterioles are not influenced by calcium channel blockade. The macula densa cells responsible for mediating tubular glomerular feedback (TGF) appears to utilize a different type of intracellular calcium mechanism for transmission of feedback signals. Increases in the intralumenal solute concentration at the macula densa elicit feedback signals to constrict the afferent arterioles and reduce glomerular pressure. These effects can be artificially induced by the intralumenal addition of calcium ionophores; however, intralumenal addition of calcium channel blockers or variation in intralumenal calcium concentration do not interfere with signal transmission. In contrast, agents that interfere with intracellular calcium mobilization can block TGF responses. Thus, intracellular mobilization of cytosolic calcium within the macula densa cells leads to transmission of TGF signals to the vascular cells. At the afferent arteriolar effector site, transmembrane calcium flux appears to serve as the dominant mechanism for regulating intracellular calcium, since TGF-mediated vasoconstrictor responses are abolished by calcium channel blockade. The efferent arterioles may be less responsive to TGF signals because of their relative insensitivity to agents that alter transmembrane calcium flux.

Keywords

Calcium Channel Blocker Renal Blood Flow Cytosolic Calcium Renal Vascular Resistance Afferent Arteriole 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Exton JH (1985) Role of calcium and phosphoinositides in the action of certain hormones and neurotransmitters. J Clin Invest 75: 1753–1757PubMedCrossRefGoogle Scholar
  2. 2.
    Williamson JR, Monck JR (1989) Hormone effects on cellular calcium fluxes. Annu Rev Physiol 51: 107–129PubMedCrossRefGoogle Scholar
  3. 3.
    Cauvin C, Loutzenhiser R, Van Breemen C (1983) Mechanisms of calcium antagonist-induced vasodilation. Annu Rev Pharmacol Toxicol 23: 373–396PubMedCrossRefGoogle Scholar
  4. 4.
    Loutzenhiser R, Leyten P, Saida K, Van Breemen C (1985) Calcium compartments and mobilization during contraction of smooth muscle. In: Graver AK, Daniel EE (eds) Calcium and contractility. Humona, pp 61–92Google Scholar
  5. 5.
    Chomdej B, Bell PD, Navar LG (1977) Renal hemodynamic and autoregulatory responses to acute hypercalcemia. Am J Physiol (Renal Fluid Electrolyte Physiol 6) 232: F490 - F496Google Scholar
  6. 6.
    Loutzenhiser R, Epstein M (1985) Effects of calcium channel antagonists on renal hemodynamics. Am J Physiol 249: F619 - F629PubMedGoogle Scholar
  7. 7.
    Navar LG, Champion WJ, Thomas CE (1986) Effects of calcium channel blockade on renal vascular resistance responses to changes in perfusion pressure and angiotensin-converting enzyme inhibition in dogs. Circ Res 58: 874–881PubMedCrossRefGoogle Scholar
  8. 8.
    Ono H, Kokubun H, Hashimoto K (1974) Abolition by calcium antagonists of the autoregulation of renal blood flow. Naunyn Schmiedebergs Arch Pharmacol 285: 201–207PubMedCrossRefGoogle Scholar
  9. 9.
    Baer PG, Navar LG (1973) Renal vasodilation and uncoupling of blood flow and filtration rate autoregulation. Kidney Int 4: 12–21PubMedCrossRefGoogle Scholar
  10. 10.
    Rosivall L, Youngblood P, Navar LG (1986) Renal autoregulatory efficiency during angiotensin-converting enzyme inhibition in dogs on a low sodium diet. Renal Physiol 9: 18–28PubMedGoogle Scholar
  11. 11.
    Ogawa N, Ono H (1988) Effect of 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8), an inhibitor of intracellular Cat’ release, on autoregulation of renal blood flow in the dog. Naunyn Schmiedebergs Arch Pharmacol 338: 293–296PubMedCrossRefGoogle Scholar
  12. 12.
    Mitchell KD, Navar LG (1990) Tubuloglomerular feedback responses during peritubular infusions of calcium channel blockers. Am J Physiol (Renal Fluid Electrolyte Physiol 27) 258: F537 - F544Google Scholar
  13. 13.
    Navar LG, Chomdej B, Bell PD (1975) Absence of estimated glomerular capillary pressure autoregulation during interrupted distal delivery. Am J Physiol 229: 1596–1603PubMedGoogle Scholar
  14. 14.
    Carmines PK, Navar LG (1989) Disparate effects of Ca channel blockade on afferent and efferent arteriolar responses to ANG II. Am J Physiol (Renal Fluid Electrolyte Physiol 25) 256: F1015 - F1020Google Scholar
  15. 15.
    Casellas D, Navar LG (1984) In vitro perfusion of juxtamedullary nephrons in rats. Am J Physiol (Renal Fluid Electrolyte Physiol 15) 246: F349 - F358Google Scholar
  16. 16.
    Steinhausen M, Baehr M (1989) Vasomotion and vasoconstriction induced by a Cat’-antagonist in the split hydronephrotic kidney. Prog Appl Microcirc 14: 25–39Google Scholar
  17. 17.
    Loutzenhiser R, Hayashi K, Epstein M (1989) Divergent effects of KCl-induced depolarization on afferent and efferent arterioles. Am J Physiol 257: F561 - F564PubMedGoogle Scholar
  18. 18.
    Lafferty HM, Gunning M, Brady HR, Brenner BM, Anderson S (1990) Renal hemodynamic and natriuretic effects of manganese and interactions with atrial natriuretic peptide. Am J Physiol (Renal Fluid Electrolyte Physiol 27) 258: F998 - F1004Google Scholar
  19. 19.
    Smith JB (1986) Angiotensin-receptor signaling in cultured vascular smooth muscle cells. Am J Physiol (Renal Fluid Electrolyte Physiol 19) 250: F759 - F769Google Scholar
  20. 20.
    Curtis JJ, Luke RG, Welchel JD, Diethelm AG, Jones P, Dustan HP (1983) Angiotensin converting enzyme inhibition in renal transplant patients with hypertension. N Engl J Med 308: 377–381PubMedCrossRefGoogle Scholar
  21. 21.
    Bell PD, Navar LG (1982) Macula densa feedback control of glomerular filtration: Role of cytosolic calcium. Miner Electrolyte Metab 8: 61–77Google Scholar
  22. 22.
    Bell PD, Franco M, Navar LG (1987) Calcium as a mediator of tubuloglomerular feedback. Annu Rev Physiol 49: 275–293PubMedCrossRefGoogle Scholar
  23. 23.
    Bell PD, Navar LG (1982) Cytoplasmic calcium in the mediation of macula densa tubuloglomerular feedback responses. Science 215: 670–673PubMedCrossRefGoogle Scholar
  24. 24.
    Bell PD, Reddington M (1983) Intracellular calcium in the transmission of tubuloglomerular feedback signals. Am J Physiol 245: F295 - F302PubMedGoogle Scholar
  25. 25.
    Bell PD (1986) Tubuloglomerular feedback responses in the rat during calmodulin inhibition. Am J Physiol 250: F715 - F719PubMedGoogle Scholar
  26. 26.
    Schnermann J, Osswald H, Hermle M (1977) Inhibitory effect of methylxanthines on feedback control of glomerular filtration in the rat kidney. Pflugers Arch 369: 39–48PubMedCrossRefGoogle Scholar
  27. 27.
    Bell PD (1985) Cyclic AMP-calcium interaction in the transmission of tubuloglomerular feedback signals. Kidney Int 28: 728–732PubMedCrossRefGoogle Scholar
  28. 28.
    Bell PD, Franco-Guevara M, Abrahamson DR, Lapointe JY, Cardinal J (1988) Cellular mechanism for tubuloglomerular feedback signalling. In: Persson AEG, Boberg U (eds) The juxtaglomerular apparatus. Elsevier, Amsterdam, pp 63–77Google Scholar

Copyright information

© Springer Japan 1991

Authors and Affiliations

  • L. Gabriel Navar
    • 1
  • Pamela K. Carmines
    • 1
  • Kenneth D. Mitchell
    • 1
  • P. Darwin Bell
    • 2
  1. 1.Department of PhysiologyTulane University School of MedicineNew OrleansUSA
  2. 2.Department of Physiology, Nephrology Research and Training CenterUniversity of Alabama at BirminghamBirminghamUSA

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